WORLD INTELLECTUAL PROPERTY ORGANIZATION
International Bureau
PCT
INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
(51) International Patent Classification 6 :
C07D 249/12, A01N 43/653, C07D
417/12, C07C 251/40
Al
(11) International Publication Number:
(43) International Publication Date:
WO 99/28305
10 June 1999 (10.06.99)
(21) International Application Number: PCT/US98/24265
(22) International Filing Date: 13 November 1998 (13.1 1.98)
(30) Priority Data:
60/067,070
1 December 1997 (01.12.97) US
(71) Applicant (for all designated States except US): E.I. DU PONT
DE NEMOURS AND COMPANY [US/US]; 1007 Market
Street, Wilmington, DE 19898 (US).
(72) Inventor; and
(75) Inventor/Applicant (for US only): WALKER, Michael, Paul
[US/US]; 22 Matthews Road, Newark, DE 19713 (US).
(74) Agent: HEISER, David, E.; £.1. Ai Pont de Nemours and
Company, Legal Patent Records Center, 1007 Market Street,
Wihgington, DE 19898 (US).
(81) Designated States: AL, AM, AU, AZ, BA, BB, BG, BR, BY
CA, CN, CU, CZ, EE, GD, GE, HR, HU, ID, IL, IS, jp|
KG, KP, KR, KZ, LC, LK, LR, LT, LV, MD, MG, MK
MN, MX, NO, NZ, PL, RO. RU, SG, SI, SK, SL, TJ, TM
TR, TT, UA, US, UZ, VN, YU, ARIPO patent (GH, GM,
KE, LS, MW, SD, SZ, UG, ZW), Eurasian patent (AM, AZ,
BY, KG, KZ, MD, RU, TJ, TM). European patent (AT, BE,
CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC,
NL, PT, SE), OAPI patent (BF, BJ, CF, CG, CI, CM, GA
GN, GW, ML, MR, NE, SN, TD, TG).
Published
With international search report.
(54) Title: FUNGICIDAL CYCLIC AMIDES
(I)
(T 1 )
Rl(0),
COOR 5
CT 2 )
r'o.
COOR*
R'Ov
oonrSrS
(Tt)
(57) Abstract
Compounds of Formula (I) and their W-oxides and agriculturally suitable salts, are disclosed which are useful as fungicides and
™ P <^N n TT n 7r iT ) ' r> ° r (T ); YZ iS 9 8™* COnsistin S ° f < a > 3 or more atoms independently selected from the
W C ' N '°' S ' S 'r i?; P T ^ n l 81 kaS i 2 ° f SBid at0mS "* C ' and (b) addition al atoms selected from H. F, CI, Br and I- R3
.s halogen, CF 3 Cj-Cs alkyl or C,-C 3 alkoxy; R4 is H, halogen, CF 3 , C,-C 3 alkyl or C,-C 3 alkoxy; and A, G, W X R> R* pj r6
and s are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula (I), a method fo'r contralllns
plant diseases caused by fungal plant pathogens which involves applying an effective amount of a compound of Formula (I) S to
controlhng arthropods which ,nvo yes contacting the arthropods or their environment with an effective amount of a compound of Formu?a
(I), and compounds of Formula (II) as denned in the disclosure and use thereof to produce compounds of Formula (I) formula
FOR THE PURPOSES OF INFORMATION ONLY
Codes used to identify States party to the PCT on the front pages of pamphlets publishing international applications under the PCT.
AL Albania
AM Armenia
AT Austria
AU Australia
AZ Azerbaijan
BA Bosnia and Herzegovina
BB Barbados
BE Belgium
BF Burkina Faso
BG Bulgaria
BJ Benin
BR Brazil
BY Belarus
CA Canada
CF Central African Republic
CO Congo
CH Switzerland
CI Cote d'lvoire
CM Cameroon
CN China
CU Cuba
CZ Czech Republic
DE Germany
DK Denmark
EE Estonia
ES
Spain
LS
Lesotho
SI
FI
Finland
LT
Lithuania
SK
FR
France
LU
Luxembourg
SN
GA
Gabon
LV
Latvia
sz
GB
United Kingdom
MC
Monaco
TD
GE
Georgia
MD
Republic of Moldova
TG
GH
Ghana
MG
Madagascar
TJ
GN
Guinea
MK
The former Yugoslav
TM
GR
Greece
Republic of Macedonia
TR
HU
Hungary
ML
Mali
TT
IE
Ireland
MN
Mongolia
UA
IL
Israel
MR
Mauritania
UG
IS
Iceland
MW
Malawi
US
IT
Italy
MX
Mexico
UZ
JP
Japan
NE
Niger
VN
KE
Kenya
NL
Netherlands
YU
KG
Kyrgyzstan
NO
Norway
ZW
KP
Democratic People's
NZ
New Zealand
Republic of Korea
PL
Poland
KR
Republic of Korea
PT
Portugal
KZ
Kazakstan
RO
Romania
LC
Saint Lucia
RU
Russian Federation
LI
Liechtenstein
SD
Sudan
LK
Sri Lanka
SE
Sweden
LR
Liberia
SG
Singapore
Slovenia
Slovakia
Senegal
Swaziland
Chad
Togo
Tajikistan
Turkmenistan
Turkey
Trinidad and Tobago
Ukraine
Uganda
United States of America
Uzbekistan
Viet Nam
Yugoslavia
Zimbabwe
WO 99/28305
PCT/US98/24265
1
TITLE
FUNGICIDAL CYCLIC AMIDES
BACKGROUND OF THE INVENTION
This invention relates to certain fungicidal cyclic amides, their TV-oxides, agriculturally
suitable salts and compositions, and methods of their use as fungicides and arthropodicides.
The control of plant diseases caused by fungal plant pathogens is extremely important
in achieving high crop efficiency. Plant disease damage to ornamental, vegetable, field,
cereal, and fruit crops can cause significant reduction in productivity and thereby result in
increased costs to the consumers. The control of arthropod pests is also extremely important
in achieving high crop efficiency. Arthropod damage to growing and stored agronomic crops
can cause significant reduction in productivity and thereby result in increased costs to the
consumer. The control of arthropod pests in forestry, greenhouse crops, ornamentals,
nursery crops, stored food and fiber products, livestock, household, and public and animal
health is also important. Many products are commercially available for these purposes, but
the need continues for new compounds which are more effective, less costly, less toxic]
environmentally safer or have different modes of action.
European Patent Application EP-A-178,826, U.S. Patent No. 5,194,662 and
U.S. Patent No. 5,286,750 disclose certain meta substituted compounds and their use as
fungicides.
SUMMARY OF THE INVENTION
This invention is directed to compounds of Formula I including all geometric and
stereoisomers, /^-oxides, and agriculturally suitable salts thereof, agricultural compositions
containing them and their use as fungicides and arthropodicides:
wherein
Tis
X-^^Ps^W Rl(O).
A — N
\2
Tl
COOR 5
T 2
WO 99/28305
PCT/US98/24265
2
N^COOR5 R1CK N^CONR6r5
T 3 or T 4 .
X is OR 1 , SCO^R 1 or halogen;
A is O, S, N, NR 5 or CR 7 ;
G is C or N; provided that when G is C, A is O, S or NR 5 and the floating double bond
is attached to G; and when G is N, A is N or CR 7 and the floating double bond is
attached to A;
W is O or S;
YZ is a group consisting of (a) 3 or more atoms independently selected from the group
C, N, O, S, Si and Ge, provided that at least 2 of said atoms are C, and
(b) additional atoms selected from H, F, CI, Br and I;
Rl is C r C 6 alkyl, C r C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl,
C 2 -C 6 haloalkynyl, C 3 -C 6 cycloalkyl, C 2 -C 4 alkylcarbonyl or C 2 -C 4
alkoxycarbonyl;
R 2 , R 5 and R 6 are each independently selected from the group H, C r C 6 alkyl, C r C 6
haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl,
Qr c 6 cycloalkyl, C 2 -C 4 alkylcarbonyl and C 2 -C 4 alkoxycarbonyl;
R 3 is halogen, CF 3 , C r C 3 alkyl or C r C 3 alkoxy;
R 4 is H, halogen, CF 3 , C r C 3 alkyl or C,-C 3 alkoxy;
R 7 is H, halogen or methyl;
m is 0, 1 or 2; and
s is 0 or 1 ;
provided that
(a) when T is T 1 , G is N, A is N, X is S(0) m Rl and m is 0; then the combination of Y
and Z is other than alkyl, haloalkyl or alkoxy;
(b) when T is T 1 , G is C and A is NR 5 ; then the combination of Y and Z is other than
alkyl or alkoxy; and
(c) when T is T 1 and R 3 is halogen, then R 4 is hydrogen.
This invention also provides compounds of Formula II including all geometric and
stereoisomers and their use as intermediates for the preparation of the fungicides and
arthropodicides of Formula I wherein
WO 99/28305
PCT/US98/24265
wherein
Tis
Tl
R ! (0) s
COOR 5
T 2
RlO^
COOR 5
RlO^
CONR6R 5
10
15
20
T 3 or T4 .
X is ORl, S(0) m Rl or halogen;
A is O, S, N, NR. 5 or CR 7 ;
G is C or N; provided that when G is C, A is O, S or NR 5 and the floating double bond
is attached to G; and when G is N, A is N or CR 7 and the floating double bond is
attached to A;
W is O or S;
Y 1 is OH, SH, OS0 2 CH 3 , OS0 2 (4-CH 3 -Ph), CHO, CH(RH)OH, CH(R")C1,
CH(R1 l)Br, CH(Rl 1)1, CH(Rl l)OS0 2 CH 3 or CH(Rl l)OS0 2 (4-CH 3 -Ph);
R 1 is C r C 6 alkyl, C r C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl,
C 2 -C 6 haloalkynyl, C 3 -C 6 cycloalkyl, C 2 -C 4 alkylcarbonyl or C 2 -C 4
alkoxycarbonyl;
R 2 , R 5 and R 6 are each independently selected from the group H, C r C 6 alkyl, C r C 6
haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl,
Qr c 6 cycloalkyl, C 2 -C 4 alkylcarbonyl and C 2 -C 4 alkoxycarbonyl;
R 3 is halogen, CF 3 , C r C 3 alkyl or C r C 3 alkoxy;
R 4 is H, halogen, CF 3 , C r C 3 alkyl or C r C 3 alkoxy;
R 7 is H, halogen or methyl;
R 1 1 is H, C r C 3 alkyl or cyclopropyl;
m is 0, 1 or 2; and
WO 99/28305
PCT/US98/24265
4
s is 0 or 1 ;
provided that when A is N, G is N, X is S(0) m Rl and m is 0, then Y 1 is other than
haloalkyl.
DETAILS OF THE INVENTION
In the above recitations, the term "alkyl", used in the compound words, such as,
"alkylthio", "haloalkylthio", "alkylsulfinyl" and "alkylsulfonyl" includes straight-chain or
branched alkyl, such as, methyl, ethyl, ^-propyl, /-propyl, or the different butyl, pentyl or
hexyl isomers. The term "alkyl", used alone or in the compound word "haloalkyl" includes
straight-chain or branched alkyl, such as, methyl, ethyl, «-propyl, /-propyl, or the different
butyl, pentyl, hexyl, heptyl, octyl, nonyl and decyl isomers. "Alkenyl" includes
straight-chain or branched alkenes such as vinyl, 1-propenyl, 2-propenyl and the different
butenyl, pentenyl and hexenyl isomers. "Alkenyl" also includes polyenes such as
1,2-propadienyl and 2,4-hexadienyl. "Alkynyl" includes straight-chain or branched alkynes
such as ethynyl, 1-propynyl, 2-propynyl and the different butynyl, pentynyl and hexynyl
isomers. "Alkynyl" can also include moieties comprised of multiple triple bonds such as
2,5-hexadiynyl.
"Alkoxy" includes, for example, methoxy, ethoxy, «-propyloxy, isopropyloxy and the
different butoxy, pentoxy and hexyloxy isomers. "Alkylthio" includes branched or
straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio,
butylthio, pentylthio and hexylthio isomers. "Alkylsulfinyl" includes both enantiomers of an
alkylsulfinyl group. Examples of "alkylsulfinyl" include CH 3 S(0), CH 3 CH 2 S(0),
CH 3 CH 2 CH 2 S(0), (CH 3 ) 2 CHS(0) and the different butylsulfinyl, pentylsulfinyl and
hexylsulfinyl isomers. Examples of "alkylsulfonyl" include CH 3 S(0) 2 , CH 3 CH 2 S(0) 2 ,
CH 3 CH 2 CH 2 S(0) 2 , (CH 3 ) 2 CHS(0) 2 and the different butylsulfonyl, pentylsulfonyl and
hexylsulfonyl isomers. "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl,
cyclopentyl, and cyclohexyl.
The term "halogen", either alone or in compound words such as "haloalkyl", includes
fluorine, chlorine, bromine or iodine. Further, when used in compound words such as
"haloalkyl", said alkyl may be partially or fully substituted with halogen atoms which may be
the same or different. Examples of "haloalkyl" include F 3 C, C1CH 2 , CF 3 CH 2 and CF 3 CC1 2 .
The terms "haloalkenyl", "haloalkynyl", "haloalkoxy", "haloalkylthio", and the like, are
defined analogously to the term "haloalkyl". Examples of "haloalkenyl" include
(C1) 2 C=CHCH 2 and CF 3 CH 2 CH=CHCH 2 . Examples of "haloalkynyl" include HCsCCHCl,
CF 3 OC, CC1 3 C=C and FCH 2 OCCH 2 . Examples of "haloalkoxy" include CF 3 0,
CC1 3 CH 2 0, HCF 2 CH 2 CH 2 0 and CF 3 CH 2 0. Examples of "haloalkylthio" include CC1 3 S,
CF 3 S, CC1 3 CH 2 S and C1CH 2 CH 2 CH 2 S.
Examples of Z include C r C 10 alkyl; C 3 -C 8 cycloalkyl; phenyl; naphthalenyl;
anthracenyl; phenanthrenyl; l//-pyrrolyl; furanyl; thienyl; l//-pyrazolyl; ltf-imidazolyl;
WO 99/28305
PCT/US98/24265
5
isoxazolyl; oxazolyl; isothiazolyl; thiazolyl; l//-l,2,3-triazolyl; 2i/-l,2,3-triazolyl;
l/M,2,4-triazolyl; 4//-l,2,4-triazolyl; 1,2,3-oxadiazolyl; 1,2,4-oxadiazolyl;
1,2,5-oxadiazolyl; 1,3,4-oxadiazolyl; 1,2,3-thiadiazolyl; 1,2,4-thiadiazolyl;
1,2,5-thiadiazolyl; 1,3,4-thiadiazolyl; l#-tetrazolyl; 2#-tetrazolyl; pyridinyl; pyridazinyl;
pyrimidinyl; pyrazinyl; 1,3,5-triazinyl; 1,2,4-triazinyl; 1,2,4,5-tetrazinyl; l//-indolyl;
benzofuranyl; benzo[6]thiophenyl; li/-indazolyl; 1/7-benzimidazolyl; benzoxazolyl;
benzothiazolyl; quinolinyl; isoquinolinyl; cinnolinyl; phthalazinyl; quinazolinyl;
quinoxalinyl; 1,8-naphthyridinyl; pteridinyl; 2,3-dihydro-l#-indenyl;
1.2.3.4- tetrahydronaphthalenyl; 6,7,8,9-tetrahydro-5#-benzocycloheptenyl;
5,6,7,8,9,10-hexahydrobenzocyclooctenyl; 2,3-dihydro-3-oxobenzofuranyl;
1 .3- dihydro- 1 -oxoisobenzofuranyl; 2,3-dihydro-2-oxobenzofuranyl;
3 .4- dihydro-4-oxo-2#- 1 -benzopyranyl; 3 ,4-dihydro- 1 -oxo- 1 #-2-benzopyranyl ;
3,4-dihydro-3-oxo-l#-2-benzopyranyl; 3,4-dihydro-2-oxo-2//-l -benzopyranyl;
4-oxo-4i/-l -benzopyranyl; 2-oxo-2#-l -benzopyranyl;
2.3.4.5- tetrahydro-5-oxo-l-benzoxepinyl; 2,3,4,5-tetrahydro-2-oxo-l-benzoxepinyl;
2.3- dihydro-l ,3-dioxo-l//-isoindolyl; 1 ,2,3,4-tetrahydro-l ,3-dioxoisoquinolinyl;
3.4- dihydro-2,4-dioxo-2//-l ,3-benzoxazinyl; 2-oxo-l ,3-benzodioxyl;
2,3-dihydro-l,l,3-trioxo-l,2-benzisothiazolyl; 9i/-fluorenyl; azulenyl; and
thiazolo[2,3-c]-l,2,4-triazolyl; each optionally substituted with R9 and optionally substituted
with one or more R 10 .
The total number of carbon atoms in a substituent group is indicated by the "Cj-Cj"
prefix where i and j are numbers from 1 to 10. For example, C r C 3 alkylsulfonyl designates
methylsulfonyl through propylsulfonyl. Examples of "alkylcarbonyl" include C(=0)CH 3 ,
C(=0)CH 2 CH 2 CH 3 and C(=0)CH(CH 3 ) 2 . Examples of "alkoxycarbonyl" include
CH 3 OC(=0), CH 3 CH 2 OC(=0), CH 3 CH 2 CH 2 OC(=0), (CH 3 ) 2 CHOC(=0) and the different
butoxycarbonyl isomers.
When a group contains a substituent which can be hydrogen, for example R 2 or R 7 ,
then, when this substituent is taken as hydrogen, it is recognized that this is equivalent to said
group being unsubstituted. When a group is optionally substituted with a substituent, for
example with R™, then, when the group is not substituted with that substituent, it is
recognized that this is equivalent to said group having a hydrogen substituent.
Compounds of this invention can exist as one or more stereoisomers. The various
stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. One
skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit
beneficial effects when enriched relative to the other stereoisomer(s) or when separated from
the other stereoisomer(s). Of note are compounds where R3 is other than fluorine and R« is
other than hydrogen and fluorine. (See, e.g., U.S. Provisional Patent Application Serial
No. 60/0579 1 7 filed September 4, 1 997, which is hereby incorporated by reference in its
WO 99/28305
PCT/US98/24265
6
entirety.) Additionally, the skilled artisan knows how to separate, enrich, and/or to
selectively prepare said stereoisomers. Accordingly, the present invention comprises
compounds selected from Formula I and agriculturally suitable salts thereof. The"
compounds of the invention may be present as a mixture of stereoisomers, individual
stereoisomers, or as an optically active form.
The salts of the compounds of the invention include acid-addition salts with inorganic
or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic,
butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric,
4-toluenesulfonic or valeric acids.
Of note are compounds where R 4 is hydrogen.
Preferred compounds for reasons of better activity and/or ease of synthesis are:
Preferred 1 . Compounds of Formula I above, and agriculturally suitable salts thereof,
wherein:
Y is -O-, -(CH 2 ) r O-, -0(CH 2 ) r -, -CHRllO-N=C(R8)-, a direct bond, -(CH 2 ) r -,
-C(Rl l)=C(Rl 1)-, -(CH 2 ) r S(0) m -, -C(R8) =N-0-CHRl 1-,
-CHRHSC(R8)=N-, -C(RU)=N-N=C(Rii)-, -CHRHO-N=C(R8)CH 2 S-,
-CHRllO-N=C(R8)CH 2 0-, -C(RH)=N-N(CH 3 )-, -CHRHOC(R8)=N-,
-CHRllOC(=S)NRH-, -CHRl lSC(=S)NRU-, -S(CHRH) r -, or
-CHRl 1 0-N=C(R 1 l)C(=N-ORl 1).; and the directionality of the Y
linkage is defined such that the moiety depicted on the left side of the
linkage is bonded to the phenyl ring having the R 3 and R 4 substituents
and the moiety on the right side of the linkage is bonded to Z;
Z is independently selected from:
i) C r C 10 alkyl, C r C 10 haloalkyl or phenyl each optionally substituted
with R 9 and optionally substituted with one or more R 10 ;
ii) a ring selected from 5 or 6-membered aromatic heterocyclic ring,
each heterocyclic ring containing 1 to 4 heteroatoms independently
selected from the group nitrogen, oxygen, and sulfur, provided that each
heterocyclic ring contains no more than 3 nitrogens, no more than 1
oxygen, and no more than 1 sulfur, each aromatic heterocyclic ring
optionally substituted with R 9 and optionally substituted with one or
more R 10 ;
iii) a naphthalene ring optionally substituted with R 9 and optionally
substituted with one or more R 10 ; and
iv) a tetrahydronaphthalene ring optionally substituted with R 9 and
optionally substituted with one or more R 10 ;
R8 is H, C r C 3 alkyl, C r C 3 alkoxy, C r C 3 alkylthio, C r C 3 haloalkyl, C 2 -C 3
alkenyl, C 2 -C 3 alkynyl, cyclopropyl, cyano or NH 2 ;
WO 99/28305
PCT/US98/24265
7
R 9 is halogen; C r C 6 alkyl; C r C 6 haloalkyl; C r C 6 alkoxy;
C r C 6 haloalkoxy; C 2 -C 6 alkenyl; C 2 -C 6 haloalkenyl; C 2 -C 6 alkynyl;
C r C 6 alkylthio; C r C 6 haloalkylthio; C r C 6 alkylsulfinyl; C r C 6
alkylsxilfonyl; C 3 -C 6 cycloalkyl; trimethylsilyl; C(=0)Ri4; C 2 -C 6
alkynyl substituted with trimethylsilyl or C 3 -C 6 cycloalkyl; or phenyl or
phenoxy, each phenyl or phenoxy optionally substituted with R 12 and
optionally substituted with one or more R 13 ;
each RIO i s halogen, C r C 6 alkyl, C r C 6 haloalkyl, C r C 6 alkoxy, C r C 6
haloalkoxy, cyano or thiocyanato; or
R 9 and an R 10 when attached to adjacent carbon atoms can be taken together
as -CH 2 CH 2 0- or -OCH 2 CH 2 0-;
each Rl 1 is independently H, C r C 3 alkyl or cyclopropyl;
R 12 is halogen, C r C 6 alkyl, C r C 6 haloalkyl, C r C 6 alkoxy,
C r C 6 haloalkoxy, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl,
C r C 6 alkylthio, C r C 6 haloalkylthio, C r C 6 alkylsulfinyl, C r C 6
alkylsulfonyl, nitro, C(=0)Rl 4 or C 3 -C 6 cycloalkyl;
each R13 i s halogen, C r C 6 alkyl, C r C 6 haloalkyl, C r C 6 alkoxy, C r C 6
haloalkoxy, cyano or thiocyanato;
R 14 is H, C r C 6 alkyl, C r C 6 haloalkyl, C r C 6 alkoxy, C r C 6 haloalkoxy; and
r is 1,2, 3 or 4.
Preferred 2. Compounds of Preferred 1 wherein:
Tis Tl;
R 3 is methyl; and
Z is phenyl each optionally substituted with R 9 and optionally substituted with
one or more R 10 ; or a 5 or 6-membered aromatic heterocyclic ring, each
heterocyclic ring containing 1 to 4 heteroatoms independently selected
from the group nitrogen, oxygen, and sulfur, provided that each
heterocyclic ring contains no more than 3 nitrogens, no more than 1
oxygen, and no more than 1 sulfur, each aromatic heterocyclic ring
optionally substituted with R 9 and optionally substituted with one or
more R 10
Preferred 3. Compounds of Preferred 2 wherein:
A is N;
Gis N;
Wis O;
XisORl;
R 1 is methyl; and
R 2 is methyl.
WO 99/28305
PCT/US98/24265
8
Preferred 4. Compounds of Preferred 1 wherein:
T is T2;
R 3 is methyl; and
Z is phenyl each optionally substituted with R 9 and optionally substituted with
one or more R 10 ; or a 5 or 6-membered aromatic heterocyclic ring, each
heterocyclic ring containing 1 to 4 heteroatoms independently selected
from the group nitrogen, oxygen, and sulfur, provided that each
heterocyclic ring contains no more than 3 nitrogens, no more than 1
oxygen, and no more than 1 sulfur, each aromatic heterocyclic ring
optionally substituted with R 9 and optionally substituted with one or
more R 10
Preferred 5. Compounds of Preferred 1 wherein:
T is T 3 ;
R 3 is methyl; and
Z is phenyl each optionally substituted with R 9 and optionally substituted with
one or more R 10 ; or a 5 or 6-membered aromatic heterocyclic ring, each
heterocyclic ring containing 1 to 4 heteroatoms independently selected
from the group nitrogen, oxygen, and sulfur, provided that each
heterocyclic ring contains no more than 3 nitrogens, no more than 1
oxygen, and no more than 1 sulfur, each aromatic heterocyclic ring
optionally substituted with R 9 and optionally substituted with one or
more R 10
Preferred 6. Compounds of Preferred 1 wherein:
T is T 4 ;
R 3 is methyl; and
Z is phenyl each optionally substituted with R 9 and optionally substituted with
one or more R 10 ; or a 5 or 6-membered aromatic heterocyclic ring, each
heterocyclic ring containing 1 to 4 heteroatoms independently selected
from the group nitrogen, oxygen, and sulfur, provided that each
heterocyclic ring contains no more than 3 nitrogens, no more than 1
oxygen, and no more than 1 sulfur, each aromatic heterocyclic ring
optionally substituted with R 9 and optionally substituted with one or
more R 10
Most preferred are compounds of Preferred 6 selected from the group:
a-(methoxyimino)-A r ,2-dimethyl-5-[[[[ 1 -[3 -
(trifluoromethyl)phenyl]ethylidene]amino]oxy]methyl]benzeneacetamideand
a-(memoxyimino)-jV,2-dimethyl-5-[[[[ 1 -[3-
(trifluoromethoxy)phenyl]ethylidene]amino]oxy]methyl]benzeneacetamide.
WO 99/28305
PC17US98/24265
9
Of note are compounds of Formula I wherein T is T 1 and R 4 is other than hydrogen.
Of note are compounds of Formula I wherein Y is -O-, -CHCRj ,)-N=C(R 8 )-, -CH 2 0-,
-0(CH 2 ) r - or -CHRl l 0 -N=C(Rl »)C(=NOR» ! >. Of note are compounds of Formula I
wherein Z is selected from the group 1,2,3,4-tetrahydrohnaphthalenyl; phenyl; naphthalenyl;
5 l#-pyrrolyl; furanyl; thienyl; l//-pyrazolyl; l#-imidazolyl; isoxazolyl; oxazolyl;
isothiazolyl; thiazolyl; l/M,2,3-triazolyl; 2//-l,2,3-triazolyl; l#-l,2,4-triazolyl;
4//-l,2,4-triazolyl; 1 ,2,3-oxadiazolyl; 1,2,4-oxadiazolyl; 1,2,5-oxadiazoIyl;
1,3,4-oxadiazolyl; 1,2,3-thiadiazolyl; 1,2,4-thiadiazolyl; 1 ,2,5-thiadiazolyl;
1,3,4-thiadiazolyl; pyridinyl; pyridazinyl; pyrimidinyl; pyrazinyl; 1,3,5-triazinyl; and
10 1 ,2 ,4-triazinyl; each group optionally substituted with R 9 and optionally substituted with one
or more R 10 . Of particular note are compounds wherein Z is phenyl, thiazolyl,
1,2,4-thiadiazolyl, pyridinyl or pyrimidinyl each optionally substituted with R 9 and
optionally substituted with one or more R 10 .
This invention also provides compounds of Formula II including all geometric and
1 5 stereoisomers which are useful as intermediates for the preparation of the fungicides and
arthropodicides of Formula I. Of note are compounds of Formula II wherein Y 1 is OH,
OS0 2 CH 3 , CHO, CH 2 OH, CH 2 C1, CH 2 Br, CH 2 I or CH 2 OS0 2 CH 3 . Of further note are
compounds of Formula II wherein T is T 1 , compounds of Formula II wherein T is T 2 ,
compounds of Formula II wherein T is T 3 or compounds of Formula II wherein T is T 4 . Of
20 particular note are compounds of Formula II wherein T is T 1 , G is N, A is N, X is OR 1 and
R 3 is methyl.
This invention also relates to fungicidal compositions comprising fungicidally effective
amounts of the compounds of the invention and at least one of a surfactant, a solid diluent or
a liquid diluent. The preferred compositions of the present invention are those which
25 comprise the above preferred compounds.
This invention also relates to a method for controlling plant diseases caused by fungal
plant pathogens comprising applying to the plant or portion thereof, or to the plant seed or
seedling, a fungicidally effective amount of the compounds of the invention (e.g., as a
composition described herein). The preferred methods of use are those involving the above
30 preferred compounds.
This invention also relates to arthropodicidal compositions comprising
arthropodicidally effective amounts of the compounds of the invention and at least one of a
surfactant, a solid diluent or a liquid diluent. The preferred compositions of the present
invention are those which comprise the above preferred compounds.
35 This invention also relates to a method for controlling arthropods comprising
contacting the arthropods or their environment with an arthropodicidally effective amount of
the compounds of the invention (e.g., as a composition described herein). The preferred
methods of use are those involving the above preferred compounds.
WO 99/28305
PCT/US98/24265
10
10
15
20
DETAILS OF THE SYNTHESIS
The compounds of Formula I can be prepared by one or more of the following methods
and variations as described in Schemes 1-44. The definitions of T, A, G, W, X, Y," Y^Y 8 , Z,
R!-R 22 , m, r and s in the compounds of Formulae 1-61 below are as defined above in the
Summary of the Invention or in the Schemes hereinafter. Compounds of Formulae Ia-Ir are
various subsets of the compounds of Formula I, and all substituents for Formulae Ia-Ir are as
defined above for Formula I.
One skilled in the art will recognize that some compounds of Formula I can exist in
one or more tautomeric forms. For example, a compound of Formula I wherein T is T 1 and
R 2 is H may exist as tautomer la or lb, or both la and lb. The present invention comprises all
tautomeric forms of compounds of Formula I where T = T 1 .
A — N
H
la
lb
The compounds of Formula I where T = T 1 can be prepared as described below in
Procedures 1) to 5). Procedures 1) to 4) describe syntheses involving construction of the
heterocycle after the formation of the aryl moiety. Procedure 5) describes syntheses of the
aryl moiety with the T-moiety already in place.
1) Alleviation Procedures
The compounds of Formula Ic, compounds of Formula I where T = T 1 , are prepared by
treating compounds of Formula 1 with an appropriate alkyl transfer reagent in an inert
solvent with or without additional acidic or basic reagents or other reagents (Scheme 1).
Suitable solvents are selected from the group consisting of polar aprotic solvents such as
acetonitrile, AT AT-dimethylformamide or dimethyl sulfoxide; ethers such as tetrahydrofuran,
dimethoxyethane, or diethyl ether; ketones such as acetone or 2-butanone; hydrocarbons such
as toluene or benzene; and halocarbons such as dichloromethane or chloroform.
WO 99/28305
PCT/US98/24265
11
Scheme 1
N
V
Z
Methods 1-4
Z
Xl=OHorSH
X = OR' orSR 1
Method 3: (R^O* BF4-
4
Method 4: (Rl) 2 S0 4 ; RIOSO2Q; or Rl-hal;
optional base
(hal = F, CI, Br, or I)
(Q = C1-C6 alkyl, 4-CH3-Ph or Ci-C 6 haloalkyl)
For example, compounds of Formula Ic, compounds of Formula I where T = T 1 , can be
prepared by the action of diazoalkane reagents of Formula 2 such as diazomethane (U = H)
or trimethylsilyldiazomethane (U = (CH 3 ) 3 Si) on compounds of Formula 1 (Method 1). Use
of trimethylsilyldiazomethane requires a protic cosolvent such as methanol. For examples of
these procedures, see Chem. Pharm. Bull. 1984, 32, 3759.
As indicated in Method 2, compounds of Formula Ic, compounds of Formula I where
T = T 1 , can also be prepared by contacting carbonyl compounds, of Formula 1 with alkyl
trichloroacetimidates of Formula 3 and a Lewis acid catalyst. Suitable Lewis acids include
trimethylsilyl triflate and tetrafluoroboric acid. The alkyl trichloroacetimidates can be
prepared from the appropriate alcohol and trichloroacetonitrile as described in the literature
(J. Danklmaier and H. Honig, Synth. Commun. 1990, 20, 203).
Compounds of Formula Ic, compounds of Formula I where T = T 1 , can also be
prepared from compounds of Formula 1 by treatment with a trialkyloxonium
tetrafluoroborate (e.g., Meerwein's salt) of Formula 4 (Method 3). The use of
trialkyloxonium salts as powerful alkylating agents is well known in the art (see U.
Schollkopf, U. Groth, C. Deng, Angew. Chem., Int. Ed. Engl. 1981, 20, 798).
WO 99/28305
PCT/US98/24265
12
Other alkylating agents which can convert compounds of Formula 1 to compounds of
Formula Ic where T = T 1 , are dialkyl sulfates such as dimethyl sulfate, haloalkyl sulfonates
such as methyl trifluoromethanesulfonate, and alkyl halides such as iodomethane and
propargyl bromide (Method 4). These alkylations can be conducted with or without
additional base. Appropriate bases include alkali metal alkoxides such as potassium
ter/-butoxide, inorganic bases such as sodium hydride and potassium carbonate, pyridine, or
tertiary amines such as triethylamine, l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and
triethylenediamine. See R. E. Benson, T. L. Cairns, J. Am. Chem. Soc. 1948, 70, 2115 for
alkylation examples using agents of this type.
Compounds of Formula la (compounds of Formula 1 wherein G = C, W = O and
X 1 = OH) can be prepared by condensation of malonates or malonate derivatives of
Formula 5 with an ambident nucleophile of Formula 6 (Scheme 2). The nucleophiles of
Formula 6 are ^-substituted hydroxylamines (HO-NHR 2 ) and substituted hydrazines
(HN(RS)-NHR 2 ). Examples of such nucleophiles are N-methylhydroxylamine and
methylhydrazine. The malonate esters of Formula 5 (E = 0(C r C 4 alkyl)) can be prepared by
methods described hereinafter. The esters of Formula 5 can also be activated by first
hydrolyzing the ester to form the corresponding carboxylic acid, and then converting the acid
into the acid chloride (E = CI) using thionyl chloride or oxalyl chloride, or into the acyl
imidazole (E = 1 -imidazolyl) by treating with 1,1 -carbonyldiimidazole.
Scheme 2
V
5
la
E = 0(C!-C 4 alkyl), CI, 1 -imidazolyl
Esters of Formula 5a can be prepared from copper (I)-catalyzed reaction of malonate
esters with substituted iodobenzenes of Formula 8 according to methods adapted from A.
Osuka, T. Kobayashi and H. Suzuki, Synthesis 1983, 67, and illustrated in Scheme 3.
WO 99/28305
PCT/US98/24265
13
Scheme 3
5a
R = Cj-C 4 alkyl
Additionally, the malonate esters of Formula 5a can be prepared by treating phenyl
acetic acid esters of Formula 9a with a dialkyl carbonate or alkyl chloroformate in the
presence of a suitable base such as, but not limited to, sodium metal and sodium hydride
(Scheme 4). For example, see J. Am. Chem. Soc. 1928, 50, 2758.
Scheme 4
O
JJ
RCT^OR
or
O
u
Cl-^^OR
base
5a
9a E 1 = OR
R = C r C 4 alkyl
Esters of Formula 9a (compounds of Formula 9 wherein E 1 is OR) can be prepared
from acid-catalyzed alcoholysis of phenyl acetonitriles of Formula 10 or by esterification of
phenyl acetic acids of Formula 1 1 as illustrated in Scheme 5 (see Org. Synth., Coll. Vol I
1941; 270).
WO 99/28305
PCT/US98/24265
14
Scheme 5
9a 11
R = C r C 4 alkyl
Phenyl acetic acid esters of Formula 9b (compounds of Formula 9a wherein Y is Y 2 )
can also be prepared by copper (I)-catalyzed condensation of phenyl halides of Formula 12
with compounds of Formula 13 as described in EP-A-307,103 and illustrated below in
Scheme 6.
Scheme 6
OR OR
R = C 1 -C 4 alkyl
9b
Y2 = -O-, -0(CH2)r, "S(CHRl l) r -
Compounds of Formula 12 can be prepared by the Arndt-Eistert synthesis starting from
benzoic acids of Formula 14 as illustrated in Scheme 7, (see F. Amdt, B. Eistert 1935, Ber.
68, 200; T. Aoyama, T. Shioiri, Tetrahedron Letters 1980, 21, 4461). For example,
treatment of benzoic acids of Formula 14 with a halogenating agent such as thionyl chloride
followed by addition of an alkylating agent such as diazomethane yields an intermediate that
can be quenched with R-OH in an appropriate solvent to afford the desired ester 12.
WO 99/28305
PCT/US98/24265
15
Scheme 7
CO2H
14
1) SOCI2, UCHN 2
2) ROH, Ag 2 0
U = H or Si (CH 3 ) 3
(a Br, I)
O
>R
12
Compounds of Formula 14 (Scheme 8) can be prepared from nitrobenzoic acids of
Formula 15 by a modification of the Sandmayer Reaction as taught in S. Kanoh, H.
Muramoto, N. Kobayashi, M. Motoi and H. Suda, Bull. Chem. Soc. Jpn. 1987, 60, 3659; M.
P. Doyle, J. Org. Chem. 1977, 42, 2426 and March, J. Advanced Organic Chemistry; 4th ed.,
John Wiley: New York, 1992; 723. Nitrobenzoic acid of Formula 15 where R3 = CH 3 and
R 4 = H is commercially available. Where R3 = R« = CH 3 the compounds can be prepared by
nitration and reduction of commercially available dimethylbenzoic acids as taught in A. N.
Fugiwars, E. M. Acton, Can J. Chem. 1970, 48, 1346.
Scheme 8
CO2H
1) reduction
2) NaN02/H+
— »
3) M+ (CI, Br, I)"
M + = Cu +
R 4
co 2 H
Some esters of Formula 9c can also be prepared by forming the Y 3 bridge using
1 0 conventional nucleophilic substitution chemistry (Scheme 9) . Displacement of an
appropriate leaving group (Lg) in electrophiles of Formula 17 or 18 with a nucleophilic ester
of Formula 16 affords compounds of Formula 9c. A base, for example sodium hydride, is
used to generate the corresponding alkoxide or thioalkoxide of the compound of Formula 16.
WO 99/28305
PCTVUS98/24265
16
Scheme 9
R = C!-C 4 alkyl
Rl4 = OH, SH, CH2OH, CH2SH
Y 3 = -O-, -OCH2-, -SCHRl 1-, -CH 2 0-, -CH 2 S(0) m -
Lg = Br, CI, I, OSO2CH3, OS0 2 (4-Me-Ph)
Compounds of Formula 16 can be prepared from compounds of Formula 12 by
methods taught in Chem. Pharm. Bull. 1985, 33 (12), 5184 or J. Org. Chem. 1988, 53 (2)
439. For example treatment of compounds of Formula 12 with a metal hydroxide, such as
sodium hydroxide, in a polar protic solvent in the presence of a metal species such as copper
5 yields compound 1 6a (compounds of Formula 1 6 where Rl4 is OH). Compounds of
Formula 16b (compounds of Formula 16 where Rl4 i s CH 2 OH or CH 2 SH) can be prepared
by metal-halogen exchange in compounds of Formula 12 followed by quenching with the
appropriate electrophile. For example, treatment of compounds of Formula 12 with a
suitable alkyllithium such as n-butyllithium in an inert solvent such as ether or
0 tetrahydrofuran (THF) followed by quenching with an electrophile such as paraformaldehyde
would yield compound of Formula 16b (where Rl4 is CH 2 OH), (see B. J. Wakefield
Organolithium Methods; Academic Press: New York; 1988). Alternatively quenching the
metalated species with a formaldehyde equivalent D-CHO (where D is (CH 3 ) 2 N, or OMe)
followed by reduction of the aldehyde with a suitable reducing agent yields compounds of
5 Formula 16b. Examples of such reducing agents are sodium borohydride (NaBH 4 ), sodium
cyanoborohydride (NaCNBH 4 ) and diisobutylaluminum hydride (DIBAL-H) (Scheme 10).
Suitable inert solvents are methanol, ethanol, methylene chloride and tetrahydrofuran, (see
M. Hudlicky, Reductions in Organic Chemistry; John Wiley & Sons: New York, 1986).
WO 99/28305
PCT/US98/24265
17
Scheme 1 0
R4
OH
id
(CI, Br, I)
R-
1) Alkyl Lithium
2) (CH 2 0) n
or D-CHO,
"reduction"
D = (Me) 2N or OCH3
Or
16b
163 12
Some esters of Formula 9d can also be prepared by forming the Y 4 bridge from
substituted hydroxylamines 16d and carbonyl compounds 19. The hydroxylamines 16d are
in turn prepared from esters 16c. Compounds of Formula 16c where the Lg is Br, CI, I,
OS0 2 CH 3 or OS0 2 (4-Me-Ph) can be prepared from compounds of Formula 16b, (see
March, J. Advanced Organic Chemistry; 3rd ed., John Wiley: New York, 1985). This
method has been described in EP-A-600,835 and is illustrated in Scheme 1 1 . Esters of
Formula 9d can be used to prepare compounds of Formula Id wherein T = T 2 or T 3 by
methods described in EP-A-600,835.
Scheme 1 1
10
15
R
o
II
19
•R8
R = Ci-C 4 alkyl
Y4 = -CHRl 10N=C(R8)-
I
OR
16c R 22 = CHRllLg
16d R 22 = CHRl 10NH 2 • HC1
2 ) Displacem ent and Conjugate Addition/Elimination Procedures
Compounds of Formula Ic, compounds of Formula I where T = T 1 , can also be
prepared by reaction of Formula 20 compounds with alkali metal alkoxides (I^OM*) or
alkali metal thioalkoxides (PJS-M+) in a suitable solvent (Scheme 12). The leaving group
Lg 1 m the amides of Formula 20 is any group known in the art to undergo a displacement
reaction of this type. Examples of suitable leaving groups include chlorine, bromine, and
sulfonyl and sulfonate groups. Examples of suitable inert solvents are
7/,//-dimethylformamide or dimethyl sulfoxide.
WO 99/28305
PCT/US98/24265
18
Scheme 12
R^O-Ivr 1 - or
Ris-ivr*-
A — N
V
20
Ic
Lg 1 = CI, Br, -S0 2 Q, or -OS0 2 Q
Q = C 1 -C 6 alkyl or C r C 6 haloalkyl
M = K or Na
X = OR ! or SR 1
Compounds of Formula 20a can be prepared from compounds of Formula lb
(compounds of Formula 1 wherein X* is OH) by reaction with halogenating agents such as
thionyl chloride or phosphorus oxybromide to form the corresponding 0-halo-substituted
derivatives (Scheme 13). Alternatively, compounds of Formula lb can be treated with an
sulfonyl halide or haloalkylsulfonyl anhydride, such as methane sulfonyl chloride,
/>-toluenesulfonyl chloride, and trifluoromethanesulfonyl anhydride, to form the
corresponding P-alkylsulfonate of Formula 20b. The reaction with the sulfonyl halides may
be performed in the presence of a suitable base (e.g., triethylamine).
Scheme 13
halogenating agent
or QS02-hal or
QSO2-O-SO2Q
lb
20a Lgl=ClorBr
20b Lgl = -OSO2Q
Q = Cj-C 6 alkyl, 4-CH3-Ph or C!-C 6 haloalkyl
hal = Br, ClorF
As illustrated in Scheme 14, sulfonyl compounds of Formula 20c (compounds of
Formula 20 where Lgl is QS0 2 -) can be prepared by oxidation of the corresponding thio
compound of Formula 21 using well-known methods for the oxidation of sulfur (see
Schrenk, K. in The Chemistry ofSulphones and Sulphoxides; Patai, S. et al., Eds.; Wiley:
New York, 1988). Suitable oxidizing reagents include meta-chloro-peroxybenzoic acid,
hydrogen peroxide and Oxone® (KHS0 5 ).
WO 99/28305
PCT/US98/24265
19
Scheme 14
Q = C { -C 6 alkyl or C^Cg haloalkyl
Alternatively, halo-compounds of Formula 20d (compounds of Formula 20 wherein
A = N, G = N, W = O and Lgl = halogen) can be prepared from hydrazides of Formula 22 a;
illustrated in Scheme 15. When Rl5 = C(=S)S(C r C 4 alkyl), the compound of Formula 22 i.
treated with excess of a thionyl halide such as thionyl chloride. The product formed first is
the ring-closed compound of Formula 23 which can be isolated or converted in situ to the
compound of Formula 20d; see P. Molina, A. Tarraga, A. Espinosa, Synthesis 1989, 923 for
a description of this process.
Alternatively, when Rl* = R2 as defined above, the hydrazide of Formula 22 is
cyclized with phosgene to form the cyclic urea of Formula 20d wherein hal = CI. This
procedure is described in detail in J. Org. Chem. 1989, 54, 1048.
WO 99/28305
PCT/US98/24265
20
Scheme 15
Rl5 = C(=S)S(C!-C4 alkyl)
22
Rl5 = C (=S)S(Ci-C 4 alkyl)
orR2
S(0)(hal) 2
N — N
\ 2
20d
, hal = CI, Br, I
The hydrazides of Formula 22 can be prepared as illustrated in Scheme 16.
Condensation of the isocyanate of Formula 24 with the hydrazine of Formula H 2 NNR 2 R 15 in
an inert solvent such as tetrahydroruran affords the hydrazide.
Scheme 16
H 2 N-N
>15
V
24
R 15 = C(=S)S(Ci-C 4 alkyl) or R2
3) Conjugate Addition/Cvclization Procedures
In addition to the methods disclosed above, compounds of Formula I wherein T is T 1 ,
X = SR 1 and G = C (Formula Ie) can be prepared by treating a ketenedithioacetal of
Formula 25 with an ambident nucleophile of Formula 6 (Scheme 17). The nucleophiles of
Formula 6 are described above.
WO 99/28305
PCT/US98/24265
10
15
21
Scheme 1 7
HA — NHR2
R16 = C(=W)0(Ci-C4alkyl)
25
Ketene dithioacetals of Formula 25a (compounds of Formula 25 wherein R!6 i s
C0 2 (C r C 4 alkyl)) can be prepared by condensing phenyl acetic acid esters of Formula 9a
with carbon disulfide in the presence of a suitable base, followed by reaction with two
equivalents of an lU-halide, such as iodomethane or propargyl bromide (Scheme 18).
Scheme 1 8
1) CS 2 , base
2) 2 equiv. Ri-CCl, Br, I)
9a
RlS -c^c^°
Ir 1 or
25a
R=C!-C 4 alkyl
Compounds of Formula lc (compounds of Formula 1 wherein A = N and G = N) can
be prepared by condensation of JV-amino-ureas of Formula 26 with a carbonylating agent
(Scheme 19). The carbonylating agents are carbonyl or thiocarbonyl transfer reagents such
as phosgene, thiophosgene, diphosgene (C1C(=0)0CC1 3 ), triphosgene
(Cl 3 COC(=0)OCCl 3 ), U'-carbonyldiimidazole, 1 , 1 '-(miocarbonyl)diimidazole, an d
l,l'-carbonylbis-l//-l,2,4-triazole. Alternatively, the carbonylating agents can be alkyl
chloroformates or dialkyl carbonates. Some of these carbonylating reactions may require the
addition of a base to effect reaction. Appropriate bases include alkali metal alkoxides such
as potassium terf-butoxide, inorganic bases such as sodium hydride and potassium carbonate,
pyridine, or tertiary amines such as triethylamine, l,8-diazabicyclo[5.4.0]undec-7-ene (DBU)
or triethylenediamine. Suitable solvents include polar aprotic solvents such as acetonitrile,
A^dimethylformamide, or dimethyl sulfoxide; ethers such as tetrahydrofuran,
dimethoxyethane or diethyl ether; ketones such as acetone or 2-butanone; hydrocarbons such
as toluene or benzene; or halocarbons such as dichloromethane or chloroform. The reaction
WO 99/28305
PCT/US98/24265
22
temperature can vary between 0 °C and 150 °C and the reaction time can be from 1 to 72
hours depending on the choice of base, solvent, temperature, and substrates.
Scheme 19
X2
1
optional base
26
lc
Q 1 and Q 2 are independently CI, OCCl 3 , 0(C r C 4 alkyl), 1-imidazolyl, 1,2,4-triazolyl
Xl = OHorSH
X2= OorS
AT-Amino-ureas of Formula 26 can be prepared as illustrated in Scheme 20. Treatment
of an aniline of Formula 27 with phosgene, thiophosgene, 1 , l'-carbonyldiimidazole, or
l,r-(thiocarbonyl)diimidazole produces the isocyanate or isothiocyanate of Formula 28. A
base can be added for reactions with phosgene or thiophosgene. Subsequent treatment of the
iso(thio)cyanate with an R 2 -substituted hydrazine produces the iV-amino-urea of Formula 26.
Scheme 20
CWCl 2 ,or R 4
W w R
optional base
N.
28
" W
R 2 — NH — NH2
w = o,s
R-
H 2 N — j{
V
26
WO 99/28305
PCT/US98/24265
23
Anilines of Formula 27a (compounds of Formula 27 where Y = Y 5 ) can be prepared
from nitro compounds of Formula 29 by reduction methods well known in the art,
Scheme 21 (see M. Hudlicky, Reductions in Organic Chemistry; John Wiley & Sons, 1986;
69-76).
Scheme 21
Y 5 = -CH2O-, -CHRl 10-N= C(R8)-,
-CH 2 S(0) m -
Compounds of Formula 29 can be prepared by contacting benzyl halides, mesylates or
tosylates of Formula 30 with various nucleophiles (Scheme 22). The appropriate alcohol or
thiol is treated with a base, for example sodium hydride, to form the corresponding alkoxide
or thioalkoxide which acts as the nucleophile.
Scheme 22
Lg = Br, CI, I, OSO2CH3, OS02(4-Me-Ph)
Compounds of Formula 30 can be prepared from corresponding nitrobenzyl alcohols of
Formula 30a (compounds of Formula 30 where the Lg group has been replaced with OH) by
reaction with halogenating agents such as thionyl chloride or phosphorus oxybromide to
form the corresponding P-halo-substituted derivatives (Scheme 23). Compounds of
Formula 30a can also be treated with an sulfonyl halide or haloalkylsulfonyl anhydride, such
as methane sulfonyl chloride, /j-toluenesulfonyl chloride, and trifluoromethanesulfonyl
anhydride, to form the corresponding P-sulfonate of Formula 30. The reaction with the
sulfonyl halides may be performed in the presence of a suitable base (e.g., triethylamine).
WO 99/28305
PCT/US98/24265
24
Scheme 23
Compounds of Formula 30a can be prepared by reduction of nitrobenzoic acids of
Formula 3 1 with a suitable reducing agent (Scheme 24), such as borane in tetrahydrofuran
dimethyl sulfide as taught in M. Pavia, W. H. Moos and F. M. Hershenson, J. Org. Chem.
1990, 55, 560, or C. F. Lane, H. L. Myatt, J. Daniels and H. B. Hopps J. Org. Chem. 1974
5 39, 3052.
O Scheme 24
31 BH3DMS
Compounds of Formula Id (compounds of Formula 1 wherein A = CR 7 , G = N, and
X 1 = O) can be prepared by the methods illustrated in Scheme 25. Ureas of Formula 32 are
reacted with activated 2-halocarboxylic acid derivatives such as 2-halocarboxylic acid
chlorides, 2-halocarboxylic acid esters or 2-haloacyl imidazoles of Formula 33. The initial
acylation on the aniline nitrogen is followed by an intramolecular displacement of the 2-halo
group to effect cyclization. Base may be added to accelerate the acylation and/or the
subsequent cyclization. Suitable bases include triethylamine and sodium hydride.
Alternatively, Formula Id compounds can be prepared by reaction of Formula 28
iso(thio)cyanates with Formula 34 esters. As described above, base may be added to
accelerate the reaction and subsequent cyclization to Formula Id compounds.
WO 99/28305
PCT/US98/24265
25
Scheme 25
Id
w = o, s
The (thio)ureas of Formula 32 can be prepared by either of the methods illustrated in
Scheme 26. The anilines of Formula 27 can be contacted with an isocyanate or
isothiocyanate of Formula 35 as described above. Alternatively, an iso(thio)cyanate of
Formula 28 can be condensed with an amine of Formula R2-NH 2 to form the urea. The
anilines and iso(thio)cyanates of Formulae 27 and 28, respectively, are commercially
available or prepared by well-known methods. For example, isothiocyanates can be prepared
by methods described in J. Heterocycl. Chem. 1990, 27, 407. Isocyanates can be prepared as
described in March, J. Advanced Organic Chemistry; 3rd ed., John Wiley: New York, 1985;
944, 1 166.
WO 99/28305
PCT/US98/24265
26
Scheme 26
W = O or S
4) Thionation Procedures
Compounds of Formula If (compounds of Formula Ic wherein W = S) can be prepared
by treating compounds of Formula Ig (compounds of Formula Ic wherein W = O) with
thionating reagents such as P 2 S 5 or Lawesson's reagent [2,4-bis(4-
5 methoxyphenyl)-l,3-dithia-2,4-diphosphetane-2,4-disulfide] as illustrated in Scheme 27 (see
Bull. Soc. Chim. Belg. 1978, 87, 229; and Tetrahedron Lett. 1983, 24, 3815).
Scheme 27
Ig X = OR 1 or SR. 1
5) Arvl Moiety Synthesis Procedures
Compounds of Formula Ih (compounds of Formula I wherein Y = Y 5 = -CH 2 0-,
-CH 2 S(0) m -, or -CHR 1 1 0-N=C(R 8 )-) can be prepared by displacing the appropriate leaving
1 0 group (Lg) in electrophiles of Formula 36 (compounds of Formula II wherein Y 1 =
CHR n Lg) with various nucleophiles (Scheme 28).
WO 99/28305
PCT/US98/24265
R \^^CHRll L g
T
36
27
Scheme 28
HO-Z, or
HO-N=C(R8)-Z, or
^
HS-Z; base
Y5 = -CH 2 0- S -CHl 10-N=C(R8)-, -CH 2 S(0) m -
Lg = Br, CI, I, OS0 2 CH 3 , OS0 2 (4-Me-Ph)
The appropriate alcohol or thiol is treated with a base, for example sodium hydride, to
form the corresponding alkoxide or thioalkoxide which acts as the nucleophile. Compounds
of Formula Ih (compounds of Formula I wherein T = T 2 and Y = is as defined in
Scheme 28) can be prepared according to methods described in the following references: for
Y5 = -(CH 2 ) r O-, EP-A-278,595 and EP-A-472,224; for Y5 = -(CH 2 ) r S(0) m -, EP-A-379,098;
for Y5 = -CHRl l0-N=C(R8)-, EP-A-370,629 and WO 94/05620. Compounds of Formula In
(compounds of Formula I wherein T = T 3 and Y = Y* is as defined in Scheme 28) can be
prepared according to methods described in the following references: for Y$ = -(CH 2 ) r O-,
EP-A-253,213, EP-A-498,188 and EP-A-554,767; for Y* = -(CH 2 ) r S(0) m -, EP-A-374^n;
for Y5 = -CHRH 0 -N=C(R8)-, EP-A-414,153, EP-A-472,300, EP-A-515,901, and
WO 92/18494.
Compounds of Formula Ii (compounds of Formula I where T is T 1 , X is OR 1 , Rl is
CH 3 , R2 is CH 3 , W is O, A is N, G is N, Y* is -O-, -0(CH 2 ) r - or -S(CHRi i) r -) can be
prepared by forming the Y 6 bridge using conventional nucleophilic substitution chemistry
(Scheme 29). Displacement of an appropriate leaving group (Lg) in electrophiles of
Formula 17 or 18 with nucleophilic compounds of Formula 37 (compounds of Formula II
wherein Yl is OH or SH, T is T 1 , G is N, A is N and the double bond is attached to A, R2 is
Me and X is OMe) affords compounds of Formula Ii. A base, for example sodium hydride,
is used to generate the corresponding alkoxide or thioalkoxide of the compounds of
Formula 37. In some cases, an additional substituent on Z which activates the leaving group
(Lg) can be advantageous (e.g., when Lg-Z is 2-chloro-3-nitrothiophene, the activating nitro
group can be removed after coupling by reduction to the amine followed by diazotization and
reduction to provide compounds of Formula Ii).
WO 99/28305
PCT/US98/24265
10
15
Rl7
R-
CH3O.
rV
28
Scheme 29
Lg-Z or
17
N— N
\
CH 3
Lg-(CHRH) r Z
18
base
CH3Q
CH3
Y6 = -o-, -0(CH 2 ) r -, "S(CHRl l) r -
37
Rl7 = OHorSH
Benzyl halides of Formula 38 can be prepared by radical halogenation of the
corresponding alkyl compound of Formula 39a, see WO 96/38425. Benzyl halides can also
be prepared by the acidic cleavage of the corresponding methyl ether of Formula 39b under
conditions which provide the halide, see Scheme 30. Methods for preparing the
corresponding compounds of Formula 38 wherein the T 1 group has been replaced by T2 are
described in WO 94/05620. Methods for preparing the corresponding compounds of
Formula 38 wherein the T 1 group has been replaced by T 3 are described in EP-A-254,426,
EP-A-299,694 and AU-A-5 5 899/90.
R 4 .
R"
Scheme 30
1) NIS, NCS or NBS, CCI4, hv
R18 = H
R 4 .
CH3O N o
XT
N CH 3
or
2) morpholine
cone. HC1, H2O
Rl8 = 0CH3
CH 3 Q^ /^-y^O
R J
N— N.
CH 3
38
39a R18 = H
39b Rl8 = OCH3
Alternatively compounds of Formula 38 can be prepared from the corresponding
alcohol of Formula 40 by reaction with halogenating agents such as thionyl chloride or
phosphorus oxybromide to form the corresponding p-halo-substituted derivatives.
Alternatively, compounds of Formula 40 can be treated with an sulfonyl halide or
haloalkylsulfonyl anhydride, such as methane sulfonyl chloride, /j-toluenesulfonyl chloride,
and trifluoromethanesulfonyl anhydride, to form the corresponding P-sulfonate of
Formula 41 . The reaction with the sulfonyl halides may be performed in the presence of a
suitable base (e.g., triethylamine) see Scheme 31.
WO 99/28305
PCT/US98/24265
29
38 Lg2 = Cl,Br
41 Lg2 = OSO2 or OS02(4-Me-Ph)
Compounds of Formula 42a wherein T = T 3 can be used to prepare compounds of
Formula Ij wherein T = T 4 and Y 4 = -CHR 1 1 0-N=C(R 8 )- according to methods described ii
EP-A-585,751 and illustrated in Scheme 32. Compounds of Formula 42a are treated with
AT-hydroxyphthalimide. Treatment of this intermediate with HNR<>R5 yields compounds of
Formula 42b wherein T 3 is converted to T 4 . Treatment of compounds of Formula 42b with
compounds of Formula 19 provides compounds of Formula Ij.
Scheme 32
O
CHR J1 ONH2
42a T = T 3 = -C(=NOR 1)-COOr5 4 2b T = T 4 = -C(=NOr1)-CONr6r5
O
R8
19
R 4 ,
Y 4
R 3
Ij Y 4 = -CHRl 1o-N=C(R 8 )-
Compounds of Formula 40 can be prepared by reducing esters of Formula 44 or
aldehydes of Formula 43 with an appropriate reducing agent, (M. Hudlicky, Reductions in
Organic Chemistry; John Wiley & Sons, 1986; 147-160). For example, diisobutylaluminum
hydride (DIBAL-H) can be used to reduce 44 in an inert solvent such as methylene chloride,
WO 99/28305
PCT/US98/24265
30
diethyl ether or tetrahydrofuran. Compounds of Formula 43 can be reduced with sodium
borohydride in a protic solvent such as methanol or ethanol, Scheme 33.
Scheme 33
R 3 ^S^ NaBH 4 ^ R 3 -^X^ DiBAL-H rS/^J
CH3CL ,N _ R -° H CH , 0 ji CH9CI?
CH30 iN 0 CHaQ^J*^
n n ft— n ft y
43
40 44
Esters of Formula 44 can be prepared from aminobenzoic acid esters of Formula 45
according to the procedures described in Scheme 34. Esters 45 can be prepared from readily
accessible aminobenzoic acids by esterification techniques well known in the art.
Scheme 34 „ 9
1) Phosgene R 3 -^"^V^
"OR
NH 2
45
3) Phosgene ft J
\
4) MeOH/NaOMe CH 3
44
Compounds of Formula 43 can be prepared by metal-halogen exchange in compounds
of Formula 46 (when R19 = ci, Br, I) with alkyllithium reagents in an inert solvent.
Quenching of the metalated species with a formaldehyde equivalent (i.e.,
JV, TV-dimethylformamide or methyl chloroformate) yields compound of Formula 43 (see
Scheme 35).
WO 99/28305
PCT/US98/24265
CH3Q
31
Scheme 35
1) Alkyl lithium
2) D-CHO
>-
H3O+
D = (Me)2N, OCH3
CHO
CH3O.
CH 3
43
CH3
46 Rl9 = Cl,BrorI
Compounds of Formula 46 are prepared from commercially available anilines of
Formula 47 according to the procedures described for the synthesis of 44, Scheme 34.
R 4 .
Scheme 36
(a Br, I)
NH 2
47
1) Phosgene
2) H2NN(CH3)2
3) Phosgene * CH 3 Q
4) CH3 OH/NaOMe
(CI, Br, I)
N — N
CH3
46
Compounds of Formula 37a (Compounds of Formula 37 where Rl7 = OH) can be
prepared by the oxidative work-up of intermediate boronic acids of Formula 48. In turn
compounds of Formula 48 can be prepared from compounds of Formula 46 by metallation
using an alkyllithium followed by quenching with a trialkoxy borane, (Scheme 37), see
Organic Synthesis via Boranes; Wiley: New York, 1975.
WO 99/28305
PCT/US98/24265
32
N — N
CH 3
37a
Alternatively compounds of Formula 37b (compounds of Formula 37 wherein
R 3 = CH 3 , R 4 = H and R 17 = OH) can be prepared according to the route outlined in
Scheme 38. Commercially available anilines of Formula 49a (where R 3 = CH 3 and P is a
protecting group) are converted to the triazolone of Formula 50 according to the procedures
5 described above. Deprotection of the oxygen followed by alcoholysis yields compounds of
Formula 37b. Alternatively compounds of Formula 49b (where R 3 = H and P is a protecting
group) are converted to the triazolone 5 1 as previously described. Metallation at the
ortho-position followed by quenching with an electrophile such as iodomethane yields
compound of Formula 52 which is deprotected to yield compound of Formula 37b,
10 Scheme 38.
WO 99/28305 PCT/US98/24265
1) "deprotect"
2) CH3 OH/NaOMe
N — N
CH 3
37b
Compounds of Formula I wherein Y is -CR n =CR n - can be prepared as illustrated in
Scheme 39. Treatment of compounds of Formula 36a (compounds of Formula 36 where Lg
is CI, Br or I) with triphenylphosphine or a trialkylphosphite produces the corresponding
phosphonium salt (Formula 53a) or phosphonate (Formula 53b), respectively. Condensation
of the phosphorus compound with a base and a carbonyl compound of Formula Z(R ! !)C=0
affords the olefin of Formula Ik. Compounds of Formula Ik wherein T = T 2 may be prepared
by methods described in EP-A-203,606, EP-A-474,042, EP-A-528,245 and FR 2,670,781.
WO 99/28305
PCT7US98/24265
34
Compounds of Formula Ik wherein T = T 3 may be prepared by methods described in
EP-A-253,213 and EP-A-254,426.
Compounds of Formula Im can be prepared from compounds of Formula Ik by
catalytic hydrogenation, see Rylander, P. N. Catalytic Hydrogenation in Organic Synthesis,
Academic Press; New York, 1979.
Scheme 39
P(0(C r C4alkyl)) 3
36a
53a R20 = P(C 6 H 5 ) 3 + (CI, Br or I) -
O
53b R 2 0 = P(O(Ci-C4alkyl))2
0=C(Rl 1)Z
base
CR n =CR n Z
Ik
Im
The olefin of Formula Ik can also be prepared by reversing the reactivity of the
reactants in the Wittig or Horner-Emmons condensation. For example, 2-alkylphenyl
derivatives of Formula 54 can be converted into the corresponding dibromo-compounds of
Formula 53a as illustrated in Scheme 40 (see Synthesis 1988, 330). The
dibromo-compounds can be hydrolyzed to the carbonyl compounds of Formula 53b, which
in turn can be condensed with a phosphorus-containing nucleophile of Formula 56 or 57 to
afford the olefins of Formula Ik.
WO 99/28305
PCT/US98/24265
R :
T
54
35
Scheme 40
1) Br 2 orNBS
2 equiv., CCI4
light
2) morpholine
cone. HC1, H2O
NBS = AMjromosuccinimide
55
55a R21 = C(Br) 2 RU
55b R21=C(=0)Rll
10
(C 6 H 5 ) 3 P=C(Rll)Z
56
or
O
M + [ ((C1-C4 alky^O^CXR 1 ] )Z ] _
57
Ik
CR. n =CR 1L Z
Oximes of Formula In (Formula I wherein Y is -C(R 8 )=N-0-CHRU-) can be prepared
from carbonyl compounds of Formula 58 by condensation with hydroxylamine, followed by
0-alkylation with electrophiles of Formula ZCHR 1 l-(Cl, Br, or I) (Scheme 41).
Alternatively, the O-substituted hydroxylamine can be condensed with the carbonyl
compound of Formula 58 to yield oximes of Formula In directly. Compounds of Formula In
wherein T = T 2 , T 3 , or T 4 may be prepared by methods described in EP-A-499,823 and
EP-A-596,254.
Scheme 4 1
C(R 8 )=0
CXR^N-OCHR 1 ^
1) H 2 N-OH
2) ZCHR 11 -(CI, Br, or I)
■ — —
or
58 H 2 N-OCHRllZ
Carbamates of Formula Io can be prepared by reacting benzyl alcohols of Formula 59
(compounds of Formula II wherein Y 1 is CH(RH)OH) with iso(thio)cyanates of Formula 60
(Scheme 42). A base such as triethylamine can be added to catalyze the reaction.
Compounds of Formula Io wherein T = T 2 , T 3 , or T 4 may be prepared by methods described
in WO 93/07116.
WO 99/28305 PCT/US98/24265
^j^^J^ CHR1
T
59
36
Scheme 42
ZNCS
60
'NHZ
Io
Compounds of Formula Ip may be prepared by methods described in EP-A-1 78,826,
EP-A-341,845 and EP-A-464,381.
Compounds of Formula Iq as defined in Scheme 43 may be prepared by methods
described in EP-A-398,692.
Scheme 43
R-
iq
ip
10
Y7 = -O-, -(CH 2 )r-, -C(Rl l)=C(Rl 1)-,
-(CH 2 )rO-, -0(CH 2 ) r , -(CH2) r S(0) n -
or-S(CHRH) r
Compounds of Formula Ir (compounds of Formula I wherein Y 8 = -O-) can be
prepared by treating compounds of Formula 61 with a triarylbismuth compound or a
substituted phenylboronic acid in the presence of cupric acetate and a tertiary amine such as
pyridine or triethylamine as illustrated in Scheme 44. The use of organobismuth reagents in
the preparation of diaryl ethers is well known in the art (see Tetrahedron Lett. 1986, 27,
3619, and Tetrahedron Lett. 1987, 28, 887). Boronic acids are well known in the literature
(see Acta Chem. Scand. 1993, 47, 221 and references therein).
Scheme 44
XT'
BiZ3
61
or (HO)2BZ
EQN, Cu(OAc)2
Y8 = -O-
WO 99/28305
PCT/US98/2426S
37
It is recognized that some reagents and reaction conditions described above for
preparing compounds of Formula I may not be compatible with certain functionalities
present in the intermediates. In these instances, the incorporation of protection/depfotection
sequences or functional group interconversions into the synthesis will aid in obtaining the
5 desired products. The use and choice of the protecting groups will be apparent to one skilled
in chemical synthesis (see, for example, Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art will recognize
that, in some cases, after the introduction of a given reagent as it is depicted in any individual
scheme, it may be necessary to perform additional routine synthetic steps not described in
1 0 detail to complete the synthesis of compounds of Formula I. One skilled in the art will also
recognize that it may be necessary to perform a combination of the steps illustrated in the
above schemes in an order other than that implied by the particular sequence presented to
prepare the compounds of Formula I.
One skilled in the art will also recognize that compounds of Formula I and the
1 5 intermediates described herein can be subjected to various electrophilic, nucleophilic,
radical, organometallic, oxidation, and reduction reactions to add substituents or modify
existing substituents.
Without further elaboration, it is believed that one skilled in the art using the preceding
description can utilize the present invention to its fullest extent. The following Examples
20 are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any
way whatsoever. Percentages are by weight except for chromatographic solvent mixtures or
where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are
by volume unless otherwise indicated. *H NMR spectra are reported in ppm downfield from
tetramethylsilane; s = singlet, d = doublet, m = multiplet and dd = doublet of doublets.
25 Coupling constants are indicated by J and reported in Hertz.
EXAMPLE 1
■ ? te P 4 l Preparation of methvl 2.5-dimethvl-q-oxobenzeneacetate
Under nitrogen, 2-bromo-p-xylene (25 g, 0.135 mol) was added dropwise to a
suspension of magnesium chips (4.25 g, 0.18 mol), 4 drops of 1 ,2-dibromoethane and an
30 iodine crystal in 1 00 mL THF at room temperature. A gradual exotherm to a gentle reflux
was noted and the reaction refluxed under nitrogen for 1 h then cooled to room temperature.
This solution was then added to a solution of oxalyl chloride (18.9 g, 0.15 mol) in 150 mL
dry THF at -65 °C with a slight exotherm noted. The reaction was stirred at this temperature
for 2 h after which time 30 mL methanol were added dropwise with a slight exotherm noted.
35 The reaction warmed to room temperature overnight.
After 1 8 h of stirring a room temperature, 1 00 mL saturated ammonium chloride were
added dropwise followed by 200 mL water. The solution was then extracted twice with
diethyl ether, washed with saturated brine, dried over magnesium sulfate and concentrated to
WO 99/28305
PCT/US98/24265
38
give an oil which was purified via column chromatography using 19: l/hexanes:ethyl acetate
as the eluent to give 1 1 . 1 g (43%) of the title compound as a pure oil. ! H NMR (CDC1 3 )
8 2.37 (s, 3H), 2.55 (s, 3H), 3.97 (s, 3H), 7.19 (d, 1H, J = 7.9Hz), 7.31( d, 1H, J = 7.7Hz),
7.46 (s, 1H).
5 Step B : Preparation of (E)-methvl a-rmemoxviminoV2.5-dimethvlbenzeneacetate
The title compound of Step A above (6.26 g, 0.0326 mol) was combined with
O-methylhydroxylamine hydrochloride (3.3 g, 0.0391 mol) in 100 mL methanol and refluxed
for 1 8 h. The reaction was then cooled to room temperature and concentrated under reduced
pressure to semi-solids which were diluted with water and extracted with methylene chloride
1 0 twice, dried over magnesium sulfate and concentrated under reduced pressure to an oil. This
crude oil was then purified via column chromatography using 19:l/hexanes:ethyl acetate as
the eluent to yield 5.80 g of a pure oil identified as the title compound. l H NMR (CDC1 3 )
8 2.14 (s, 3H), 2.33 (s, 3H), 3.87 (s, 3H), 4.05 (s, 3H), 6.91(s, 1H), 7.13 (s, 2H).
Ste P C : Preparatio n of (^-methyl 5-(bromomemvlVa-(methoxvimmo)-2-
15 methvlbenzeneacetate
The title compound from Step B above (5.80 g, 0.0262 mol) was combined with
AT-bromosuccinimide (5.61 g, 0.0315 mol) and 10 mg of benzoyl peroxide in 100 mL carbon
tetrachloride and refluxed 5 h under nitrogen. The reaction was then cooled to room
temperature and concentrated under reduced pressure to an oil which was purified via
20 column chromatography using 1 : 1 :8/ethyl acetate:THF:hexanes as the eluent to yield 0.40 g
of pure, title compound as an oil. l H NMR (CDC1 3 ) 8 3.9 (s, 3H), 4.1(s, 3H), 4.5 (s, 2H),
7.1-7.2 (m, 1H), 7.2-7.3 (m, 1H), 7.45(s, 1H).
Ste P D: Preparation of CfiVmethvl a-(methoxviminoV2-methvl-5-rrrri-r3-
(trifluoro methvDphenvnethvlidenelaminoloxvlmethvnbenzeneacetate
25 1 -[3-(Trifluoromethyl)phenyl]ethanone oxime (0.30 g, 0.00 1 5 mol) and sodium
hydride (0.06 g of 60%, 0.0015 mol) were combined at room temperature in 30 mL
N, N-dimethylformamide and stirred for 1 h. Then the title compound from Step C above
(0.40 g, 0.00133 mol) was added with no exotherm. The reaction was stirred at room
temperature for 1 8 h. The reaction was diluted with ice-water and extracted with diethyl
30 ether twice, washed with saturated brine and dried over magnesium sulfate. The solvent was
removed under reduced pressure to give an oil which was purified via column
chromatography using 4:l/hexane:ethyl acetate to yield 0.13 g of pure, title compound as an
oil. 1H NMR (CDC1 3 ) 8 2.19 (s, 3H), 2.27 (s, 3H), 3.86 (s, 3H), 4.04 (s, 3H), 5.23 (s, 2H),
7.15 (d, 1H, J=1.7Hz), 7.25 (m, 1H), 7.37 (dd, 1H, J=1.7, 7.3Hz), 7.5 (m, 1H), 7.6 (d, 1H,
35 J=7.8Hz), 7.84 (m, 1H), 7.89 (d, 1H, J=0.5).
WO 99/28305
PCT/US98/24265
39
EXAMPLE 2
Ste P A: Preparation of r^-methvl a-fmethoxvmemvleneV2.5-dimethvlbenzeneacetate
Under nitrogen, methoxymethyl triphenylphosphonium chloride (24 g, 0.07 rhol) was
added portion-wise to a solution of potassium ferr-butoxide (7.8 g, 0.07 mol in 300 mL dry
5 diethyl ether at 5 °C. The reaction then stirred at room temperature for 1 h. Then the title
compound from Example 1, Step A above (1 1.1 g, 0.0578 mol) was added and the reaction
stirred at room temperature for 1 8 h. The reaction was washed with water, dried over
magnesium sulfate and concentrated to an oil. This crude oil was then purified via column
chromatography using 4:l/hexanes:ethyl acetate to yield 1.9 g of pure title compound as an
10 oil. 1H NMR (CDC1 3 ) 5 2.13 (s, 3H), 2.31 (s, 3H), 3.70 (s, 3H), 3.82 (s, 3H), 6.92 (s, 1H),
7.02 (d, 1H, J=7.7), 7.1 1 (d, 1H, J=7.7), 7.55 (s, 1H).
Ste P B: Preparation of CEVmet hvl 5-fbromomethvlVa-fmethoxvmethvleneV2-
methvlbenzeneacetate
The title compound from Step A above (Example 2) (1.9 g, 0.0086 mol ),
15 JV-bromosuccinimide (1.54 g, 0.0086 mol) and 10 mg of 2,2'-azobisisobutyronitrile (AIBN)
were combined in 40 mL carbon tetrachloride and refluxed under nitrogen for 6 h, cooled to
room temperature and concentrated to an oil. The crude oil was then purified via column
chromatography using 4:l/hexanes:ethyl acetate as the eluent to give 0.10 g oil of the title
compound. lH NMR (CDC1 3 ) 5 3.7(s, 3H), 3.8 (s, 3H), 4.45 (s, 2H), 7.1 (s, 1H), 7.2-7.3 (m,
20 2H), 7.6 (s, 1H).
£ te P C: Preparatio n of CfiVmethyl a-fmethoxvmethvlene')-2-methvl-5-rrrri-r3-
ftrifluorom ethvnphenvnethvlidenelaminoloxvlmethvllbenzeneacetate
l-[3-(Trifluoromethyl)phenyl]ethanone oxime (0.075 g, 0.00037 mol) and sodium
hydride (0.02 g of 60%, 0.00037 mol) were combined at room temperature in 10 mL DMF
25 and stirred for 1 h. Then the title compound from Step B (Example 2) above (0.10 g,
0.00034 mol) was added with no exotherm. The reaction was stirred at room temperature for
1 8 h. The reaction was diluted with ice-water and extracted with diethyl ether twice, washed
with saturated brine and dried over magnesium sulfate. The solvent was removed under
reduced pressure to give an oil which was purified via column chromatography using
30 1 : l/hexane:ethyl acetate to yield 0. 1 3 g of pure, title compound as an oil. l H NMR (CDC1 3 )
8 2.19 (s, 3H), 2.26 (s, 3H), 3.69 (s, 3H), 3.80 (s, 3H), 5.22 (s, 2H), 7.17 (s, 1H), 7.25 (m,
1H), 7.5 (m, 1H), 7.6 (m, 2H), 7.8 (m, 1H), 7.91 (d, 1H, J=0.5).
By the procedures described herein together with methods known in the art, the
following compounds of Tables 1 to 10 can be prepared. The following abbreviations are
35 used in the Tables which follow: / = tertiary, / = iso, Me = methyl, Et = ethyl, Pr = propyl,
z-Pr = isopropyl, Bu = butyl, OMe = methoxy, SMe = methylthio and CN = cyano.
WO 99/28305
PCT/US98/24265
40
Structure for Table 1
Z
Structure for Tables 2a, 2b and 2c
Structure for Table 3a. 3b and 3c
Z
H 3 CO
C0 2 CH 3
Structure for Table 5a, 5b and 5c
CH30.
"N" ^C»NHCH3
Structure for Tables 7a. 7b. 7c and 7d
H3C XJT>-
Structure for Tables 9a. 9b. 9c and 9d
Rl2 6 JR13
5
R3
H3C
N— N
N CH3
Structure for Table 4a. 4b and 4c
1
R-
H3CO, „
"N -CO2CH3
Structure for Tables 6a. 6b. 6c and 6d
Structure for Tables 8a. 8b. 8c and 8d
Rl2 6 Rl3
r3 >y^ N ^ N
Structure for Table 10
WO 99/28305
PCT/US98/24265
41
Table 1
R3
Y
Column 1
Colinnn 2
CH 3
-O-
Z =
3-CF 3 -phenyl
4-Me-2-thiazolyl
CH 3
-O-
z =
3-CF 3 -2-pyridinyl
5-phenyl-2-thiazolyl
CH 3
-O-
z =
4-CF 3 -phenyl
4-phenyl-2-thiazolyl
CH 3
-O-
z =
4-CF3-2-pyridinyl
3-phenoxyphenyl
CH 3
-O-
z =
5-Me-2-thiazolyl
phenyl
CI
-O-
z =
3-CF3-phenyl
4-Me-2-thiazolyl
CI
-O-
z =
3-CF 3 -2-pyridinyl
5-phenyl-2-thiazolyl
CI
-O-
z =
4-CF 3 -phenyl
4-phenyl-2-thiazolyl
CI
-O-
z =
4-CF 3 -2-pyridinyl
3-phenoxyphenyl
CI
-O-
z =
5-Me-2-thiazolyl
phenyl
CF 3
-O-
z =
3-CF3-phenyl
4-Me-2-thiazolyl
CF 3
-o-
z =
3-CF 3 -2-pyridinyl
5-phenyl-2-thiazolyl
CF 3
-o-
z =
4-CF 3 -phenyl
4-phenyl-2-thiazolyl
CF 3
-o-
z =
4-CF 3 -2-pyridinyl
3-phenoxyphenyl
CF 3
-O-
z =
5-Me-2-thiazolyl
phenyl
CH 3
-CH 2 0-N=C(CH 3 )-
z =
3-CF 3 -phenyl
4-Me-2-thiazolyl
CH 3
-CH 2 0-N=C(CH 3 >
z =
3-CF 3 -2-pyridinyl
5 -phenyl-2-thiazoly 1
CH 3
-CH 2 0-N=C(CH 3 )-
z =
4-CF3 -phenyl
4-phenyl-2-thiazolyl
CH 3
-CH 2 0-N=C(CH 3 )-
z =
4-CF 3 -2-pyridinyl
3-phenoxyphenyl
CH 3
-CH 2 0-N=C(CH 3 )-
z =
5-Me-2-thiazolyl
phenyl
CI
-CH 2 0-N=C(CH 3 )-
z =
3-CF 3 -phenyl
4-Me-2-thiazolyl
CI
-CH 2 0-N=C(CH 3 )-
z =
3-CF 3 -2-pyridinyl
5 -phenyl-2-thiazoly 1
CI
-CH 2 0-N=C(CH 3 )-
z =
4-CF 3 -phenyl
4-phenyl-2-thiazolyl
CI
-CH 2 0-N=C(CH 3 )-
z =
4-CF 3 -2-pyridinyl
3-phenoxyphenyl
CI
-CH 2 0-N=C(CH 3 )-
z =
5-Me-2-thiazolyl
phenyl
CF 3
-CH 2 0-N=C(CH 3 )-
z =
3-CF 3 -phenyl
4-Me-2-thiazolyl
CF 3
-CH 2 0-N=C(CH 3 )-
z =
3-CF 3 -2-pyridinyl
5-phenyl-2-thiazolyl
CF 3
-CH 2 0-N=C(CH 3 )-
z =
4-CF 3 -phenyl
4-phenyl-2-thiazolyl
CF 3
-CH 2 0-N=C(CH 3 >
z =
4-CF 3 -2-pyridinyl
3 -phenoxyphenyl
CF 3
-CH 2 0-N=C(CH 3 )-
z =
5-Me-2-thiazolyl
phenyl
CH 3
-C(CH 3 )=N-CH 2 -
z =
3-CF 3 -phenyl
4-Me-2-thiazolyl
CH 3
-C(CH 3 )=N-CH 2 -
z =
3-CF 3 -2-pyridinyl
5-phenyl-2-thiazolyl
CH 3
-C(CH 3 )=N-CH 2 -
z =
4-CF 3 -phenyl
4-phenyl-2-thiazolyl
CH 3
-C(CH 3 )=N-CH 2 -
z =
4-CF 3 -2-pyridinyl
3-phenoxyphenyl
CH 3
-C(CH 3 )=N-CH 2 -
z =
5-Me-2-thiazolyl
phenyl
WO 99/28305
PCT/US98/24265
42
R3
Y
Column 2
CI
-CfCHi^N-CHo-
3 -C F3 -phenyl
4-Me-2-tniazolyl
CI
-C(CH 3 )=N-CH2-
'/ —
3-CF^-2-pyndinyl
5-pnenyJ-2-tniazolyl
CI
-C(CH 3 )=N-CH2-
'/ —
*t-i_r ^ -pnenyi
4-phenyl-2-thiazolyl
CI
-C(CH 3 )=N-CH?-
z =
4 - f"" 1 P" "» - — T\ uri H i »*i \r 1
3 -phenoxypheny l
CI
-C(CH 3 )=N-CH 2 - •
z =
5-Me-2-thiazolyl
phenyl
CF 3
-C(CH 3 )=N-CH 2 -
z =
3-CF 3 -phenyl
4-Me-2-thiazolyl
CF 3
-C(CH 3 )=N-CH2-
z =
3-CF 3 -2-pyridinyl
5-phenyl-2-thiazolyl
CF 3
-C(CH 3 )=N-CH 2 -
z =
4-CF 3 -phenyl
4-phenyl-2-thiazolyl
CF 3
-C(CH 3 )=N-CH 2 -
z =
4-CF 3 -2-pyridinyl
3-phenoxyphenyl
CF 3
-C(CH 3 )=N-CH 2 -
z =
5-Me-2-thiazolyl
phenyl
Table 2a
R 3 = CH 3
Y
Column 1
Column 2
-O-
y —
rnenyi
3-OMe-phenyl
-O-
Z -
■ 3 -pnenyi
3-Me-phenyl
-O-
Z =
3-F-phenyl
3-OCF 3 -phenyl
-O-
z =
4-Me-phenyl
3-I-phenyl
-O-
z =
3-SCH 3 -phenyl
2-Me-phenyl
-O-
z =
3-SCHF2-phenyl
4-SCH 3 -phenyl
-O-
z =
3-cyclohexyl-phenyl
4-SCHF 2 -phenyl
-O-
z =
6-CF 3 -2-pyridinyl
5-CF 3 -2-pyridinyl
-O-
z =
4-CF 3 -2-pyridinyl
6-Me-2-pyridinyl
-O-
z =
6-(CF 3 CH 2 0)-4-pyrimidinyl
5-Me-2-pyridinyl
-0-
z =
2-(CF 3 CH20)-4-pyrimidinyl
4-(CF 3 CH 2 0)-2-pyrimidinyl
-O-
z =
4-Me-2-pyridinyl
3,5-diMe-phenyl
-O-
z =
2-naphthalenyl
5,6,7,8-tetrahydro-2-
naphthalenyl
-O-
z =
4-OCF 3 -phenyl
3-/-Bu-phenyl
-O-
z =
4-f-Bu-phenyl
6-(CF 3 CH 2 0)-2-pyra2inyl
-O-
z =
3-SCF 3 -phenyl
4-SCF 3 -phenyl
-O-
z =
4-CF 3 -6-Me-2-pyridinyl
3-CN-phenyl '
-O-
z =
4,6-diMe-2-pyridinyl
3,5-di(CF 3 )-phenyl
-O-
z =
5-Cl-2-thiazolyl
5-I-2-thiazolyl
-O-
z =
5-OCF 3 -2-thiazolyl
5-(CH 3 ) 3 Si-2-thiazolyl
-O-
z =
5-CN-2-thiazolyl
5-SCH 3 -2-thiazolyl
WO 99/28305
PCT/US98/24265
43
Y
Column 1
Column 2
-0-
Z =
5-CF 3 -2-thiazolyl
4-Me-5-Cl-2-thiazolyl
-O-
Z =
4-Me-5-I-2-thiazolyl
4-Me-5-CN-2-thiazolyl
-O-
Z =
4-Me-5-CF 3 -2-thiazolyl
-o-
Z =
3-(HC=C)-phenyl
3-(CH 3 CsC)-phenyl
-o-
Z =
3-((CH 3 ) 3 CC=C)-phenyl
3-((CH 3 ) 3 SiC=C)-phenyl
-o-
Z =
3-(t>— C=C>phenyl
5-Me-2-thienyl
-o-
Z =
5-(CH 3 ) 3 C-2-thienyl
5-Cl-2-thienyl
-o-
Z =
5-Br-2-thienyI
5-I-2-thienyl
-o-
Z =
4-Me-2-thienyl
4-fCHi^aC-2-thienvl
-o-
Z =
4-Cl-2-thienyl
4-Br-2-thienvl
-o-
Z =
4-I-2-thieny]
■ )•' tuivxc ^ until y i
-o-
z =
4-Me-5-Cl-2-thienyl
4-Me-5-Br-2-thienv1
-o-
z =
4-Me-5-I-2-thienyI
3-Cl-2-thienvl
-o-
z =
5-Me-3-thienyl
S-fCH-jI'aC-S-thienvl
-o-
z =
5-Cl-3-thienyl
5-Br-3-thienyl
-o-
z =
5-I-3-thienyl
4-Me-3-thienyl
-o-
z =
4-(CH 3 ) 3 C-3-thienyl
4-Cl-3-thienyl
-O-
z =
4-Br-3-thienyl
4-I-3-thienyl
-o-
z =
4,5-diMe-3-thienyl
4-Me-5-Cl-3-thienyl
-o-
z =
4-Me-5-Br-3-thienyl
4-Me-5-I-3-thienyl
-o-
z =
2-Cl-3-thienyl
2-CF^-Dhenvl
-CH 2 0-
z =
Phenyl
3-CF 3 -phenyl
-CH 2 0-
z =
2-Me-5-/-Pr-phenyl
2-Me-4-OCH 3 -phenyl
-CH 2 0-
z =
4-OCF 3 -phenyl
2-Me-5-CF 3 -phenyl
-CH 2 0-
z =
3-OCHF 2 -phenyl
4-OCHF 2 -phenyl
-CH 2 0-
z =
3,5-di(CF 3 )-phenyl
2-Me-4-OCHF 2 -phenyl
-CH 2 0-
z =
6-CF 3 -2-pyridinyl
3-OCF 3 -phenyl
-CH 2 0-
z =
4-CF 3 -2-pyridinyl
4-Me -2 -py ridiny 1
-CH 2 0-
z =
2-Me-4-OCFo-phenyl
5-^/fe-2-r)vrirfinvl
— ' J— Wj A Hill IV 1
-CH 2 0-
z =
3,6-diMe-2-pyridinyl
5 -CF 3 -2-pyridinyl
-CH 2 0-
z =
4,6-diMe-2-pyridinyl
6-OCF 3 -2-pyridinyl
-CH 2 0-
z =
4-CF 3 -6-Me-2-pyridinyl
3-Me-2-pyridinyl
-CH 2 0-
z =
4-Cl-2-pyrimidinyl
6-Me-2-pyridinyl
-CH 2 0-
z =
4-Cl-2-pyrimidinyl
3-Et-phenyl
-CH 2 0-
z =
2,6-diMe-4-pyridinyl
2,4,6-triMe-phenyl
-CH 2 0-
z =
3-Cl-2-pyridinyl
6-Cl-4-pyrimidinyl
WO 99/28305
PCTAJS98/24265
44
Y
Column 1
Column 9
-CH 2 0-
Z =
1 -naothalenvl
2,3,6-triMe-phenyl
-CH 2 0-
z =
6-Cl-2-Dvrazinvl
*+-v^r 3 -z-pynnuuinyx
-CH 2 0-
z =
S-CFo -4-Dvrimidinvl
-t-* -rr-pnenyi
-CH 2 0-
z =
3 -Me-2 -pyridinyl
*f~^i-*i -pynoiny 1
-OCH 2 -
z =
2 -M e-Dhenvl
2,5-diMe-phenyl
-OCH 2 -
z =
3-CF-i-phenvl
-OCH 2 -
z =
4— Mc-ph eny 1
A t Hit nkanul
-13 u-pneny 1
-OCH 2 -
z =
3-Cl-nhenvl
*f-oi-pnenyJ
-OCH 2 -
2 =
3-NBu-phenyl
-OCH 7 -
J.
z =
*> iiapiiuiaivii y i
1 -naphthaleny 1
-OCH 2 -
2 =
J p y a luiiiy i
4-pyridinyl
-OCHo-
Z -
fi— A/f p- 9 — n\/f"i H i mi\
\j ivic .c— ^jynuuiyi
tetrahydro)naphthalenyl
-CH 2 0-N=C(CH 3 )-
z =
J -IV1C- JJUCIljrl
4-Cr3-pnenyI
-CH 2 0-N=C(CH 3 )-
z =
3-ci-pnenyl
-CH 2 0-N=C(CH 3 )-
z =
4-Br-nhpnvl
-Jjj-ai^r^j-pnenyi
-CH 2 0-N=C(CKh)-
Z =
4-OCHF^ -nhprvl
~ v^^xur2 puciiyi
4-/-Bu-phenyI
-CH 2 0-N=C(CH 3 )-
Z =
3-f-Bu-nhetivl
5-CF3-2-pyndinyl
-CH 2 0-N=C(CH 3 )-
Z =
4-OCF-j -nhenvl
-CH 2 0-N=C(CH,)-
Z =
5 -^^e-2-ovri di nvl
*r-^r 3-o-jvie--i-pyriQinyi
-CH 2 0-N=C(CH 3 )-
z =
4-Me-2 -pyridinyl
*t, o~uuvie--fc-pynciiny 1
-CH 2 0-N=C(CH 3 )-
z =
6-Me-2-nvridinvl
1T *v -t. jjj" i luuiy i
6-CF3 -2-pyndinyl
-CH 2 0-N=C(CH 3 )-
z =
6-OMe-2 -pyridinyl
2 fi-diTVfp-4-fivridinvl
-CH 2 0-N=C(CH 3 )-
z =
2.6-diCl-4-nvridiTiv1
-»-vj^r ^ -z-pyncimy 1
-CH 2 0-N=C(CH 3 )-
z =
4-0^4e-2-nvridinvl
£ r-^'^r'3'-z-pyncunyi
-CH 2 0-N=C(CH 3 )-
z =
5-OCHF->-2-nvridinvl
o-ucr 0 -z-pynainyi
-CH 2 0-N=C(CH 3 )-
z -
4-OCHFi-nvriHinvl
j 3 i_-H2*J jpnenyi
-CH 2 0-N=C(CH 3 )-
z =
6-OCHF->-2-nvrir1invl
3-Et-ph.enyl
-CH 2 0-N=C(CH?V
z =
1 - tin r^htViQ lf>n\/l
1- llaJJilUlalCllyl
1 ,2,3.4- tetranyaro-2-
naphthalenyl
-CH 2 0-N=C(CH 3 )-
z =
3-SMe-phenyl
3 -ethvnvlnhenvl
imf VU1T j JpAIVUJ 1
-CH 2 0-N=C(CH 3 )-
z =
f-Bu
2-F-5-CF 3 -phenyl
-CH=N-OCH(CH 3 >
z =
4-CF 3 -phenyl
3-CF 3 -phenyl
-CH=N-OCH(CH 3 >
z =
4-OCF 3 -phenyl
3-OCF 3 -phenyl
-CH=N-OCH(CH 3 )-
z =
3-Cl-phenyl
4TCl-phenyl
-CH=N-OCH(CH 3 )-
z =
3,5-diCl-phenyl
3,5-di(CF 3 )-phenyl
-CH=N-OCH(CH 3 )-
z =
3-Me-phenyl
4-Me-phenyl
WO 99/28305
PCT/US98/24265
45
Y
Column 1
-CH=N-OCH(CH 3 )-
z =
2-nanhthalenv]
*• mtpiui ioivuy i
^-wL^ri-r 2 "Phenyl
-CH=N-OCH(CH 3 )-
z =
j v_»v_^i- j.i 2 jJiiciiyj
^-cr^-z-pynainyl
-CH=N-OCH(CH 3 )-
z —
-> v^r j~z-pynuinyi
o-Cr3-2-pynainyl
-CH=N-OCH(CH->)-
z =
4— "M"p-9-TivrifHnvl
■ ivi.c a> -py i luuiy i
5 -Me -2-py ridiny 3
-CH=N-OCH(CH 3 )-
z =
v\ — nA P— 7 — nvn H i n \t 1
u ivic £• pyiitimyi
4-Cr 3 -o-Me-2-pynainyl
-CH=N-OCH(CH 3 )-
z =
4-DPF-. -^.nvrirlimrl
t-u^ij -z-pynauiyi
5 -OCr 3 -2-pynamyl
-CH=N-OCH(CHo)-
z =
n— Oi'F^ — 7-rivri H in \i\
v v-* v-'A j*i."uyiiumyi
'J-vJCtlb 2 -2-pynainyl
-CH=N-OCH(CH 3 )-
z =
6-OCHF 2 -2-pyndinyl
-CH=N-OCH(CH 3 )-
z =
j-i-d u-pnenyi
4-/-Bu-phenyl
-CH 2 -SC(Et)=N-
z =
3-CF 3 -phenyl
-CH 2 -SC(Et)=N-
z =
*t- r 3 -pneny i
3-OCF 3 -pnenyl
-CH 2 -SC(Et)=N-
z
^-Pl-nhpnvl
4-Cl-pnenyl
-CH 2 -SC(Et)=N-
7 =
^ ^-HiP1-r»Vif»ti\/l
j , j ui^. i-pneny i
3,5-ai(CF 3 )-phenyl
-CH?-SC(Et)=N-
z =
j -ivic-piiciiy i
4-Me-phenyl
-CH 7 -SC(Et)=N-
z =
j,_>-uiivic-pnenyi
2-napntnalenyI
-CH 2 -SC(Et)=N-
z =
o-ivie-z-pynuinyi
4-Me-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
4 h— Hl\^P— "J T\\rri AirwA
*t,u uuvic-z-pyriuinyi
5-Cl-2-pynainyl
-CH 2 -SC(Et)=N-
z =
uiv^i-z-pyriuinyi
5-Me-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
S— f^F*> — V— nvTir1in\/l
v-i ^ *> pyiiumyi
3-r>r-D-JVie-z-pynainyl
-CH 2 -SC(=S)NMe-
z =
4-CF'> -nhenvl
3-CF 3 -phenyl
-CH 2 -SC(=S)NMe-
z =
4-OPF-» -nhenvl
~ vvv^x j pixciiy i
j-ui^r 3 -piieiiyi
-CH 2 -SC(=S)NMe-
z =
4-ci-pnenyi
-CH 2 -SC(=S)NMe-
z =
j,3-Qi(Cr 3 )-pnenyl
-CH 2 -SC(=S)NMe-
z =
j i vie piiviiyi
4-Me-phenyl
-CH 2 -SC(=S)NMe-
z =
-» j j uj-ivj.c*piiciiyi
2-naphthalenyl
-CH 2 -SC(=S)NMe-
z =
fi— AyTf* — y — nvW H i ni/l
v j.vj.c pyiiuuiyi
4-Me-2-pyndinyl
-CH 2 -SC(=S)NMe-
z =
~jU uuvic i uyiiuuiyi
j-t-i-z-pynainyi
-CH 2 -SC(=S)NMe-
z =
4 6-diCI-2-nvridinvl
5-Me-2-pyndinyl
-CH 2 -SC(=S)NMe-
z =
w-i <£» pyi luuiyi
j-t>r-o-Me-2-pynauiyl
-CH 2 SC(SMe)=N-
z -
-j~i.vi.c~piicii.yi
4-Me-phenyl
-CH 2 SC(SMe)=N-
z =
3,5-diMe-phenyl
3-Cl-nhenvl
-CH 2 SC(SMe)=N-
z =
4-Cl-phenyl
3,5-diCl-phenyl
-CH 2 SC(SMe)=N-
z =
3-CF3-phenyl
4-CF 3 -phenyl
-CH 2 SC(SMe)=N-
z =
3-OCF 3 -phenyl
4-OCF 3 -phenyl
-CH 2 SC(SMe)=N-
z =
3,5-di(CF 3 )-phenyl
CH 2 CH 2 -/-Bu
-CH 2 SC(SMe)=N-
z -
r-Bu
2-naphthalenyl
-CH 2 SC(SMe)=N-
z =
6-Me-2-pyridinyl
4-Me-2-pyridinyl
WO 99/28305
PCT/US98/24265
46
Y
VsV/JlUJllJl 1
column z
-CH 2 SC(SMe)=N-
z =
4 fS-di\4e-9-r>vri dinvl
5-Cl-2-pyridinyl
-CH 2 SC(SMe)=N-
z =
4 fi-difl-^-nvriHifivl
5 -Me-2 -pyridiny I
-CH 2 SC(SMe)=N-
z =
5-CFi -2-nvridinvl
j-ur-o-ivie-z-pynainyl
-CH 2 S-
2 =
x -lvie -pneny i
3-CF 3 -phenyl
-CH 2 S-
7 -
/I f * Li mm am* rl
H-\^r 5-pnenyi
2,5-diMe-phenyl
-CH 2 S-
2 =
z-ci-pnenyi
3-Cl-pnenyj
-CH->S-
z
7 =
z-v^i-pnenyi
2,5-diCl-phenyl
-CH 2 S-
2 =
4, 6-diMe-2 -pyrimidiny 1
4-Me-l,2,4-tnazol-3-yl
-CH 2 S-
2 =
z-iidpnmaienyi
1 -Me-2-imidazolyl
-CH->S-
7 =
4-Me-2-pyrimidinyl
5-Me- 1 ,3 ,4-thiadiazol-2-y 1
-CH70-N=CrcHo')CHoS-
7 —
3 -Me-pheny 1
2-Me-phenyl
-CHoO-N=CCCH-i , >CH-><;-
7 —
j-Cr^-pnenyl
4-CF 3 -phenyl
-CH'iO-N=CfCH-5'>CHi < ;-
/ _
/J —
j-^i-pnenyl
2-Et-phenyl
-CHoO-N=CCCHa"»CH'.«;-
7 —
*f-i^i-pnenyl
2-naphthalenyl
-CH 2 0-N=C(CH 3 )CH 2 S-
2 =
x , j-uuvic -pneny i
4-CF 3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )CH 2 0-
7 =
o -ivie-pneny i
2-Me-phenyl
-CH 7 0-N=C(CH*)CH->0-
7 =
4-Me-phenyI
3-CF 3 -phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
2 =
**~v_-r3-pnenyi
4-Cl-phenyl
-CH 2 0-N=C(CHi)CH->0-
2 =
3-PI-nhpnvl
j v^i -jjuoii y 1
j,3-uiMe-pnenyl
-CH 2 0-N=C(CH->)CH-jO-
2 -
uuvic-pncnyi
2-Me-5-/-rr-pnenyl
-CH 2 0-N=C(CH*)CH?0-
2 -
o-Urj-z-pynainyl
-CH 2 0-N=C(CH 3 )CH 9 0-
2 =
■ 3 *t"pyiiuiiiyi
D-Cr3-z-pynainyl
-CH 2 O-N=C(CH 3 )CH 2 0-
z =
6-^4e-2-nvridinv1
j -ivie-z-py nciiny i
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4-Vf e-2-n vri d i n vl
i -napnuiaienyi
-CH 2 0-N=C(CHt.)CHoO-
Z =
2-n anhth a 1 ph\/I
z-tr 3 -pneny I
-CH 2 CH->-
z z
2 =
0_\/Tp_r\hf»Ti\/l
z,5-aiMe-pneny!
-CH 2 CH 2 -
2 =
v^r^-pncnyi
4-Cr3-pnenyl
-CH 2 CH 7 -
2 =
3-Cl-nhenvl
*r-^i-pnenyi
-CH 2 CH->-
z =
— ' KsKjI "J pi iuiiy 1
4-ULr 3-pnenyI
z z
2 =
y_Ki t.nnnmil
z-Me-5-CI-pnenyI
-CH 2 CH 2 -
z =
2-naphthalenyl
j^u-uuvit-x-pyiiumyi
-CH=C(CH 3 )-
z =
3-Me-phenyl
4-Me-phenyl
-CH=C(CH 3 )-
z =
3,5-diMe-phenyl
3-Cl-phenyl
-CH=C(CH 3 )-
z =
4-Cl-phenyl
3-OCF 3 -phenyl
-CH=C(CH 3 )-
z =
4-OCF 3 -phenyl
3-CF 3 -phenyl
-CH=C(CH 3 )-
z =
4-CF 3 -phenyl
2-naphthalenyl
-CH=C(CH 3 )-
z =
4-CF 3 -2-pyridiny 1
6-CF 3 -2-pyridinyl
WO 99/28305
PCT/US98/24265
47
Y
Column 1
-CH=N-N=C(CH 3 )-
Z-
3-Mc-phenyl
4-Me-phenyl
-CH=N-N=C(CH 3 )-
z =
3-CFo-ohenvI
^-Ur3-pnenyi
-CH=N-N=C(CH 3 )-
z =
3-OCTP ^ -nhpnvl
^-L/ur3-pnenyi
-CH=N-N=C(CH 3 )-
2 =
j» j uiivie-pnenyi
3-Cl-phenyl
-CH=N-N=C(CH 3 >
z =
3,5-diCl-phenyl
-CH=N-N=C(CH 3 )-
2 -
4—1^ M** _ / tii rfi f\\ n\ t\
^ pynuinyi
5-CF 3 -2-pyndinyl
-CH=N-N=C(CHO-
2 =
^ v-'i ^ ^ py 11 ciinyi
4-Me-2-pyridinyl
-CH=N-N=C(CH 3 )-
2 =
S — — 0 — V Ft H 1 T» \ A
■j xvxt, A,-pyiiuiiiyi
6-Me-2-pyridinyl
-CH=N-N=C(CH 3 )-
z =
2 — n a r» li t \\ a 1 **r» \r 1
z. uajjiiLiiaiciiyj
4,6-diMe-2-pyndmyl
-CH=N-N=C(CH 3 )-
2 -
X _Th t-nnomrl
j-ci-pnenyi
/-Bu
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
2 =
j -ivie-pncnyi
4-Me-phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
2 =
j , j -uiivi e-pneny I
3-Cl-phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
2 =
*t-^i -pneny i
3,5-diCl-phenyl
-CH 2 0-N=C(CH 3 )C(=NOCHh)-
2 =
J v^r ^ -pnenyi
4-CF 3 -phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH^)-
2 =
j)j ui^r t j ~ u li ci i y i
3-OCr 3 -phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
2 =
4-OCF i -nh en vl
Lrl 3
-CH 2 0-N=C(CH 3 )C(=NOCHo)-
2 -
f-Bu
^-napntnalenyl
-CH 2 0-N=C(CH 3 )C(=NOCHi)-
2 =
4- /-Rii-r*liAnv1
« * uu piiciiyi
4-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH-j)-
z =
-/ .c. pyiiiimyi
6-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-CFi -2-nvrtHinvl
j -\^r 3 -z-pynamyi
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z-
6-CF i -2-t) vri din vl
4,6-diMe-2-pyndiiiyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-CFo -2-nvrim iHinvl
6-CF3 -2-pyrimidinyl
-CH=N-N(CH 3 )-
v J'
Z =
3-Me-nhenvl
4-Me-ph.enyl
-CH=N-N(CH 3 >
Z =
3,5-diMe-phenyl
^ -i—i-pnciiy 1
-CH=N-N(CH 3 )-
Z =
4-Cl-phenyl
j , j -uiv^ 1 -pneny 1
-CH=N-N(CH 3 )-
Z =
3-CF 3 -phenyl
T-i^r 3 -pnenyi
-CH=N-N(CH 3 )-
z =
3-OCFi-Dhenvl
*r-vJL/r3-piienyj
-CH=N-N(CH 3 )-
2 =
2-nanhthalenvl
i mi/iiiiimvlij i
4 -/-Bu-pheny 1
-CH=N-N(CH 3 )-
2 =
*r-ivi.c-^ py nuiny i
5-Me-2-pyndinyl
-CH=N-N(CH 3 )-
2 -
u-ivic -jt-py nciiny i
4-CF 3 -2-pyridinyl
-CH=N-N(CH 3 )-
Z =
5-CF3 -2-pyridinyl
6-CF a -2-DVridinvl
-CH=N-N(CH 3 )-
Z =
4,6-diMe-2-pyridinyl
4-CF 3 -2-pyrimidinyl
-CH 2 OC(SMe)=N-
Z =
4-CF3-phenyl
3-CF 3 -phenyl
-CH 2 OC(SMe)=N-
Z =
4-OCF3-phenyl
3-OCF 3 -phenyl
-CH 2 OC(SMe)=N-
Z =
3-Cl-phenyl
4-Cl-phenyl
-CH 2 OC(SMe)=N-
Z =
3,5-diCl-phenyl
3-Me-phenyl
-CH 2 OC(SMe)=N-
Z =
4-Me-phenyl
3,5-diMe-phenyl
WO 99/28305
PCT/US98/24265
48
Y
Column 1
fnliiTrm 9
-CH 2 OC(SMe)=N-
Z =
2-naphthalenyl
u-ivie -z-pynuiiiyi
-CH 2 OC(SMe)=N-
Z =
4-Me-2-pyridinyl
*t , u-uuvie-z -pynumy i
-CH 2 OC(SMe)=N-
Z =
5-CF 3 -2-pyridinyl
j ivic -i-py nuiny i
-CH 2 OC(=S)NMe-
Z =
4-CF3 -phenyl
a— f ' p a _T*h on\/l
-CH 2 OC(=S)NMe-
Z =
4-OCF 3 -phenyl
3-OCF-» -nhenvl
-CH 2 OC(=S)NMe-
Z =
3-Cl-phenyl
4-C1 -nhpnvl
-CH 2 OC(=S)NMe-
z =
3,5-diCl-phenyl
3-\fle-r>hf*tivI
-CH 2 OC(=S)NMe-
z =
4-Me-phenyl
9 aiivic-pneny 1
-CH 2 OC(=S)NMe-
z =
2-naphthalenyl
D-ivie-z-pynainyi
-CH 2 OC(=S)NMe-
z =
4-Me-2-pyridinyl
j v- uuvie-z ~py n amy i
-CH 2 OC(=S)NMe-
z =
5-CF 3 -2-pyridinyl
IVrt ^ — /.nun /H 1 /l
ivie-A-pyiiuiiiyi
-SCH 2 -
z =
2-Me-phenyl
uiiYAc-piiciiy 1
-SCH 2 -
z =
3 -CF3 -phenyl
4-CF3 -phenyl
-SCH 2 -
z =
4-Me-phenyl
t-(-i5 u-pneny i
-SCH 2 -
z =
3-Cl-phenyl
*+-\_, i-p ncny 1
-SCH 2 -
z =
2-Me-5-Cl-phenyl
u-pncnyi
-SCH 2 -
z =
2-naphthalenyl
1 nonhtlin 1 ami il
1 -napninaienyi
-SCH 2 -
z =
3-Dvridinvl
4-pyndinyl
-SCH 2 -
z =
6-Me-2-pyridinyl
S ft 7 R_tf»trci \^\n\rr\-'J
/ ,0-lCUaIiyUTU—
Tinn ri+rin 1 am rl
iiapxiinaieiiyi
-CH 2 ON=C(SCH,)-
z =
3-CF*j -nhenvl
v-zi^r 3 -pnenyi
-CH 2 0-N=C(SCH 3 )-
z =
3-Me-nhenvl
^r-^r 3 -pnenyi
-CH 2 0-N=C(SCH 3 )-
z =
4-OCF 3 -phenyl
4-Me-phenyl
-CH 2 0-N=C(SCH-,)-
z =
3-Cl-nhenvl
j»j-uid-pnenyi
-CH 2 0-N=C(cyclopropyl)-
z =
3 -CFo -phenyl
3-OCF^-nhpnvI
-CH 2 0-N=C(cyclopropyl)-
z =
3-Me-phenyl
-CH 2 0-N=C(cyclopropyl)-
z =
4-OCF 3 -phenyl
4-Me-phenyl
-CH 2 0-N=C(cyclopropyl)-
z =
3-Cl-phenyl
3,5-diCl-phenyl
Table 2b
= C1
Y
Column 1
Column 2
-O-
z =
Phenyl
3-OMe-phenyl
-O-
z =
4-CF 3 -phenyl
3-Me-phenyl
-O-
z =
3-F-phenyl
3-OCF 3 -phenyl
-O-
z =
4-Me-phenyl
3-I-phenyl
WO 99/28305
PCT/US98/24265
49
Y
Column 1
Column 2
-O-
z =
3-SCH 3 -phenyl
2-Me-phenyl
-O-
z =
3-SCHF 2 -phenyl
4-SCHi -nhenvl
-o-
z =
3-cyclohexyl-phenyl
4-SCHF2-phenyl
-o-
z =
6-CF-i-2-pyridinyI
5-CFi-2-ovridinv1
-o-
z =
4-CF-i-2-pyridinyl
6-M"e-2-nvridinvl
v Aviv U f A Y X
-o-
z =
6-(CFoCHoO)-4-pyriinidinyl
5 -Me-2 -py ridiny 1
-o-
z =
2-(CF 3 CH 2 0)-4-pyrimidmyl
4-f CFi CHoOl -2-nvrtm i dim/1
-o-
z =
4-Mc-2-pyridinyl
-o-
z =
2-naphthalenyl
5 6 7 8-tetrahvdrn-?-
nanh th a 1 f*n vl
-o-
z =
4-OCF->-phenyl
3-/-Bu-nVieriv1
-o-
z =
4-f-Bu-phenyl
-o-
z =
3-SCF 3 -phenyl
-o-
z =
4-CF^-6-Me-2-Dvridinvl
-o-
z =
4, 6-diMe-2-pyridinyl
-o-
z =
5-Cl-2-thiazolyl
5-1-2 -thia7olvl
-o-
z =
5-OCF 3 -2-thiazolyl
-o-
z =
5-CN-2-thiazolyl
5-SCH 3 -2-thiazolyl
-o-
z =
5-CF 3 -2-thiazolyl
4-Me-5-Cl-2-thiazolyl
-o-
z =
4-Me-5-I-2-thiazolyl
4-Me-5-CN-2-thiazolyl
-o-
z =
4-Me-5-CF 3 -2-thiazolyl
-o-
z =
3-(HC=C)-phenyl
3-(CH 3 C=C)-phenyl
-0-
z =
3-((CH 3 ) 3 COC)-phenyl
3-((CH 3 ) 3 SiC=C)-phenyl
-0-
z =
3-( O-C^Q-phenyl
5-Me-2-thienyl
-o-
z =
5-(CH 3 ) 3 C-2-thienyl
5-Cl-2-thienyl
-o-
z =
5-Br-2-thienyl
5-I-2-thienyl
-o-
z =
4-Me-2-thienyl
4-(CH 3 ) 3 C-2-thienyl
-o-
z =
4-Cl-2-thienyl
4-Br-2-thienyl
-0-
z =
4-I-2-thienyl
4 5-diMe-2-thienv1
-0-
z =
4-Me-5-Cl-2-thienyl
4-Me-5-Br-2-thienyl
-o-
z =
4-Me-5-I-2-thienyl
3-Cl-2-thienyl
-o-
z =
5-Me-3-thienyl
5-(CH 3 ) 3 C-3-thienyl
-o-
z =
5-Cl-3-thienyl
5-Br-3-thienyl
-o-
z =
5-I-3-thienyl
4-Me-3-thienyl
-O-
z -
4-(CH 3 ) 3 C-3-thienyl
4-Cl-3-thienyl
-o-
z =
4-Br-3-thienyl
4-I-3-thienyl
WO 99/28305
PCT/US98/24265
50
Y
Column 1
Column 0
-O-
z -
4 5-diMe-3-thienv1
4-Mf»-S-C1-^-thipn\/l
'T~ivic~j~v-/i"j~iiiicnyi
-O-
Z =
4-Me-5-Br-3-thienvl
4-Mp-S-T-^-thipTivi
^ i»ic~ j~Liiiciiyi
-o-
z =
2-Cl-3-thienyl
-CH 2 0-
z
z =
Phenyl
j ■ v^r 3-pnenyi
-CH 2 0-
Z
z =
2-Me-5-f-Pr-'nhenv1
z -ivic-H- v^v^-ri^ pnciiyi
-CH 2 0-
Z
z =
4-OCFo -ohenvl
z-ivic- j -v^r 3 -pncnyi
-CH 2 0-
Z
z -
3-OCHF-)-ohenvl
" v_/v_/i ii 2 piicnyi
-CH 2 0-
z =
3 5-difCF-jVnhenvl
z-ivie^-ijv^riP2"pnenyi
-CH 2 0-
2 =
fi— CP** — 7 — TWl-lfiitll/l
\3 V^I "2 ^ pyllVJlliy I
-CH 2 0-
z =
4-CP l ^-'5-T\\7riHin\7i
*r-i_-r a -z-py noiny 1
4-Me-2 -pyridiny 1
-CH->0-
z =
5-Me-2-pyndinyl
-CH 2 0-
z -
J»w uiivxc - i — Liyi juiiiy 1
J-Lf 3-Z-pyTiainyi
-CH 2 0-
z =
^ > u-uiivi e-z-pyniimy 1
O-UL^r 3-z-pynainyl
-CHoO-
Z
z =
• 3 u ivic-^-pynuiiiyi
3 -Me-2 -pyridiny 1
-CHbO-
z =
4-C1 — *? — t^vri m \fK in vr1
• vi py 1 uiiiuiuy 1
6-Me-2-pyridinyl
-CH 2 0-
z =
4 — C 1 — 7 —iwri i /4 1 n i / 1
• \si "jl pyiuiiiuiiiyi
3-Et-phenyl
-CH 2 0-
z =
^,v)~uiivic~*T~pyi lumyi
2 ,4,6-trilVIe-pheny 1
-CH 2 0-
z =
3-C1-9-nvriHinv1
o~v-*i-*r-pyi lrniuiiiyi
-CH 2 0-
z -
1 -nant h^ilptivl
-l ~ucip uiaiGiiy 1
z , j , 0- uuvie-pncny 1
-CH 2 0-
z =
6- CI -2 -nvraTi n vl
V >w A ^> t/Y k ft Ci I.J 1 Jr A
H-v^r 3 -z -pyniuioinyi
-CH 2 0-
Z
z =
6-CF-5— 4-Tivrimidinvl
J — t — P r"— n n (*Tl \f I
* 1 1 -piivuy i
-CH 2 0-
Z
z =
3-Me-2-Dvridinvl
4-C 1 -9 -n vri e\ i n vt
-OCH 2 -
z
z =
2-Me-Dhenvl
? - I \A ri i»n\/l
Zi j j uiivic^piiciiy 1
-OCH 2 -
z =
3-CF 3 -phenyl
4-CF 3 -phenyl
-OCH 2 -
z
z =
4-Me-phenyl
4-/-T5i 1 -?> h (*nvl
-OCH 2 -
z =
3-Cl-Dhenvl
t w —piici ly 1
-OCH 2 -
z =
^ -/ -DU-pneny 1
-OCH 2 -
z
z =
2 -naohthalenvl
i "liapiiuiaidt y l
-OCH 2 -
z =
>-nvnniTivl
j pyiiuiiiyi
4-pyndinyl
-OCH->-
z =
vi ivic ^ pyiiuiuy*
A 7 c
Z-(,D,0,/,»-
icu any ux (J jnapuuuaicliy 1
-CH 2 0-N=C(CH 3 )-
z =
3-Me-phenyl
4-CF3 -phenyl
-CH 2 0-N=C(CH 3 )-
z =
3,5-diMe-phenyl
3-Cl-phenyl
-CH 2 0-N=C(CH 3 )-
z =
4-Br-phenyl
3,5-di(CF 3 )-phenyl
-CH 2 0-N=C(CH 3 )-
z =
4-OCHF 2 -phenyl
4-r-Bu-phenyl
-CH 2 0-N=C(CH 3 )-
z =
3-/-Bu-phenyI
5-CF3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )-
z =
4-OCF 3 -phenyl
3-OCHF2-phenyl
WO 99/28305
PCTAJS98/24265
51
Y
Column 1
Column 9
-CH 2 0-N=C(CH 3 )-
Z =
5-Me-2-pyridinyl
^ wr 3 u lvic 4. pyntiiny i
-CH 2 0-N=C(CH 3 )-
Z =
4-Me-2-pyridinyl
•t, u uiivxc nuinyi
-CH 2 O-N=C(CH-0-
Z -
V iTiW U VtlUUlYl
6-CF 3 -2-pyndiiiyl
-CH 2 0-N=C(CH 3 )-
Z =
6-OMe-2-pyridinyl
2,6-diMe-4-pyridinyl
-CH 2 0-N=C(CH 3 )-
Z =
2.6-diCl-4— nvridinvl
^-f^r^TT^ O rn/riilini;!
j~vjv^_r 3 - - t-pynainyi
-CH 2 0-N=C(CH 3 )-
z =
4- 0\^f*- *? -nvriH i rwi\
• wjtic £. -pyiituiiyi
1-UL.r 3 -z-pynainyl
-CH 2 0-N=C(CH 3 )-
z =
5 -O PHF^ - 7 -n vri d i n vl
o- uur 3 -^-pynainy i
-CH 2 0-N=C(CH 3 )-
z =
4-OPHF^ -n vri d i nvl
3 L,rl 2 L))pnenyl
-CH 2 0-N=C(CH 3 )-
z =
U"WV/Xir 2 pynuinyi
j-Jit-pnenyl
-CH90-N=CfCH-jV
2 =
i -iidpninaicnyi
l,2,3,4-tetranydro-2-
naphthalenyl
-CH->0-N=C(CH?V
2 =
3-SMe-phenyl
3-ethynylphenyl
-CH 2 0-N=C(CH 3 )-
z -
/-Bu
^-r-D-i_r 3 -pnenyl
-CH=N-OCH(CH 3 >
Z -
4-PF-* -r*ti<»Tivl
~ v_-i 2 pucuyi
j-Cr 3 -pnenyl
-CH=N-OCH(CH 3 )-
z =
4-OCFo -nhpnvl
i-ULr 3 -pnenyl
-CH=N-OCH(CH 3 )-
z =
3-P1-nhenvl
n-ci-pnenyi
-CH=N-OCH(CH 3 )-
z =
3 5-diCl-nhenvl
W-dULt 3 }-pnenyi
-CH=N-OCH(CH*)-
z =
3-\^e-r>henvl
A nil A nnAm rl
T—ivic-pnciiyi
-CH=N-OCH(CH*)-
z =
2-naohtha lenvl
** ~ w unr 2 p iiciiy i
-CH=N-OCH(CH 3 )-
z =
3-OCHFi-nhenvl
H-i^r a-z-pyriainyi
-CH=N-OCH(CH 3 )-
z =
5 -PF*» -2 -twri din vl
o*-^,r ^-z-pyriainyi
-CH=N-OCH(CH 3 )-
z =
4-Me-2 -nvridinvl
•?~ivic-^-pYiiuiiiyi
-CH=N-OCH(CH 3 )-
z =
6-Me-2-Dvridi nvl
*T-^-.r ^ -o-ivie-z-pynuiny i
-CH=N-OCH(CH 3 )-
z =
^-vjv^r ^ -z-pynQuiyi
-CH=N-OCH(CH 3 )-
6-OCF*2-2-Dvridinvl
" v^v^rxro ^ pyritiinyi
-CH=N-OCH(CH 3 )-
z =
5-OCHFo-2-nvriHinvl
o-UL*rir 2~^~pynainyi
-CH=N-OCH(CHo>
z =
3 -/-Bu-nh en vl
*T-f-ou-pneiiyi
-CH 2 -SC(Et)=N-
z =
4— PF -> — r>h vl
3 -CF^ -phenyl
-CH 9 -SC(Et)=N-
z =
4- OC F i -n h en vl
j-tJUr ^-pnenyi
-CH 2 -SC(Et)=N-
z -
*#-L4-pnenyj
-CH 2 -SC(Et)=N-
z =
3,5-diCl-phenyl
3 S-difCF-aVohenvI
-CH 2 -SC(Et)=N-
z =
3-Me-phenyl
4-Me-phenyl
-CH 2 -SC(Et)=N-
z =
3,5-diMe-phenyl
2-naphthalenyl
-CH 2 -SC(Et)=N-
z =
6-Me-2-pyridinyl
4-Me-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
4,6-diMe-2-pyridinyl
5-Cl-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
4,6-diCl-2-pyridinyl
5-Me-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
5-CF 3 -2-pyridinyl |
5-Br-6-Me-2-pyridinyl
WO 99/28305
PCT/US98/24265
52
Y
Column 1
i^oiuirin Z
-CH 2 -SC(=S)NMe-
Z =
4~CF''»- , nhf*Tlv1
j-tr 3 -phenyl
-CH 2 -SC(=S)NMe-
z =
4-OCFo-nhenvl
j"ULr 3 -pnenyl
-CH 2 -SC(=S)NMe-
z =
3-Cl-nhenvl
^f-d-pnenyi
-CH 2 -SC(=S)NMe-
z =
3 5-diCI-nhenvl
— 'j— * uiv^i uiibiiy i
j , 3 -ai^Cr 3 j-pneny 1
-CH 2 -SC(=S)NMe-
z =
-J-iVlC-pilCliy 1
4-Me-phenyI
-CH 2 -SC(=S)NMe-
z =
^ lVif <a nnantil
» uuvic-piicny i
2-naphthalenyl
-CH 2 -SC(=S)NMe-
z =
o-ivic-z-pyiiuiiiyi
4-Me-2-pyndinyl
-CH 2 -SC(=S)NMe-
z =
t, u- uiivie-z-pyn uinyi
5-Cl-2-pyndiny]
-CH 2 -SC(=S)NMe-
z =
*t,o~ai^i-z-pynainyi
5-Me-2-pyridinyl
-CH 2 -SC(=S)NMe-
z =
j-v^r'^-z-pynuinyi
5-Br-6-Me-2-pyndinyl
-CH 2 SC(SMe)=N-
z =
^ _\/f r»_r*Vii"»T"i\/l
*J pilCIiyi
4-Me-pnenyl
-CH 2 SC(SMe)=N-
z =
j» j uuvie-pncnyi
3-Cl-phenyl
-CH->SC(SMe)=N-
z =
4— i 1— T^Vif>n\/l
^ v^i— piicuy l
3 , 5-diCl-phenyl
-CH 2 SC(SMe)=N-
z —
x" 3-pnenyj
4-CF 3 -phenyl
-CH 2 SC(SMe)=N-
z =
4-vJCr 3-pnenyl
-CH 2 SC(SMe)=N-
z =
3 5-difCF-jVDhenvl
v>ri2 ^J^2 -* -oil
-CH 2 SC(SMe)=N-
z =
f-Bu
2-naphthalenyl
-CH 2 SC(SMe)=N-
z =
6-*^e-2-T>vri H in vl
4-Me-2-pyndinyl
-CH 2 SC(SMe)=N-
z =
4 6-diN4f?-2-nvriHinvl
5-Cl-2-pyndinyl
-CH 2 SC(SMe)=N-
z =
4.6-diCl-2-nvridinv1
5 -Me-2-pyndiny 1
-CH 2 SC(SMe)=N-
z =
5-CFi -2-T)vridinv1
j -xji-o-ivic-z -pyncinyi
-CH 2 S-
z =
V— ftrt **— M Jl **n\/1
1 Vi.c pilCIly 1
3-Cr3-pnenyl
-CH 2 S-
z =
4_r^P-i „nVi*»n\/l
*t-\^r 2 -puenyi
2,5-diMe-pnenyl
-CH 2 S-
z =
2 -F t-iVh f»n vl
J-Cl-pnenyl
-CH 2 S-
z =
2-P1-r»Vif*nv1
2,5-aiCl-pnenyl
-CH 2 S-
z =
■> v"uiivxc""^~pjf i mil uinyi
4-Me- 1 ,2,4-tnazoi-3-yl
-CH 2 S-
z =
9 — nn n h t/Vi n 1 ativ 1
iia^JlluiaJCUyi
J -Me-2-imidazolyl
-CH 2 S-
z =
u-luiA- /_nt n*i rvi « /-I « «■ r 1
^~ivic-z.-pyijjHiiiinyji
5-Me- 1 ,3,4-thiadiazol-2-yl
-CH 2 0-N=C(CH-i)CHiS-
■fa V "/ X
z =
■j -ivic-piivuy i
2-Me-pnenyl
-CH 2 0-N=C(CH 3 )CH 2 S-
7 =
3-CF3 -phenyl
4-CF3 -phenyl
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
3-Cl-phenyl
2-Kt-nh en vl
■fa uiiwiiy ft
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
4-Cl-phenyl
2-naphthalenyl
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
2,5-diMe-phenyl
4-CF 3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
3-Me-phenyl
2-Me-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4-Me-phenyl
3-CF 3 -phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4-CF3-phenyl
4-Cl-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
3-Cl-phenyl
3,5-diMe-phenyl
WO 99/28305
PCT/US98/24265
53
Y
• Column 1
Pnlnmn 0
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
2,5-diMe-phenyl
z -ivie- ->-/ -rr-pneny i
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
3-Et-phenyl
-CH 2 O-N=C(CH 3 )CH 2 0-
Z =
4-CF 3 -2-pyridinyl
j-^r^ ^ -pynainyj
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
6-Me-2-pyridinyl
^ — - "y — 1\ vri rl i n \/ 1
-CH 2 0-N=C(CH 3 )CH 2 O-
Z =
4-Me-2-pyridinyl
1 -IldpilLilalCIiy I
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
2-naphthalenyl
z-i_.r 2 -pnenyi
-CH 2 CH 2 -
Z =
2-Me-phenyl
2,5-diMe-phenyl
-CH 2 CH 2 -
Z =
3-CF 3 -phenyl
4-CF3-phenyl
-CH 2 CH 2 -
Z-
3-Cl-phenyl
*t~^ i-pneny 1
-CH 2 CH 2 -
Z =
3-OCF 3 -phenyl
t r~wv-^r'5 -pnenyi
-CH 2 CH 2 -
Z =
2-Et-phenyl
z-ivic-j-^i-pnenyi
-CH 2 CH 2 -
Z =
2 -naphthaleny 1
3 , 6-diMe-2-pyndinyI
-CH=C(CH 3 )-
Z =
3 -Me-nhenvl
4-Me-phenyl
-CH=C(CH 3 )-
Z =
3,5-diMe-phenyl
•j-^i-pnenyi
-CH=C(CH 3 )-
z =
4-Cl-phenyl
->-wv^r 3 -pnenyi
-CH=C(CH 3 )-
z =
4-OCFi-Dhenvl
j - Lr 2 "pnenyi
-CH=C(CH 3 )-
z =
4-CF 3 -phenyl
z-jidpnuiaienyi
-CH=C(CH 3 )-
z =
4-CF 3 -2-pyridinyl
u-v^r^j-z—pyouiliyi
-CH=N-N=C(CH 3 )-
z =
3-Me-phenyl
t-ivic-piiciiyi
-CH=N-N=C(CH 3 )-
z =
3-CF 3 -phenyl
*t-v*-.r 2 pnenyi
-CH=N-N=C(CH 3 )-
z =
3-OCF 3 -phenyl
H-uLr 3 -pnenyi
-CH=N-N=C(CH 3 )-
z -
3.5-diMe-r»henvl
j-ci-pnenyi
-CH=N-N=C(CH 3 )-
z =
4-Cl-phenyl
->,j-aiL^i-pnenyi
-CH=N-N=C(CH 3 )-
z =
4-CF j a-2-Dvridinvl
->-^r 3 'Z-pynoinyi
-CH=N-N=C(CH 3 )-
z =
6-CF 3 -2-pyridiny I
**~ivie -£. -pynamy i
-CH=N-N=C(CH 3 )-
z =
5-Me-2-pyridinyl
J —-nx rt*t /lint rl
o-ivie~Z"pyriaiiiyi
-CH=N-N=C(CH 3 )-
z =
2-naphthalenyl
ujuvxc-z "uy I luiny l
-CH=N-N=C(CH 3 )-
z =
3-Et-phenyl
t-DU
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
3-Me-phenyl
*T"ivic-pncuyi
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
3,5-diMe-phenyl
j-v^ i-pneny i
-CH 2 O-N=C(CH 3 )C(=N0CH 3 )-
z =
4-Cl-phenyl
3,5-diCl-phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
3-CF 3 -phenyl
4-CF3 -phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
3,5-di(CF 3 )-phenyl
3-OCF 3 -phenyI
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-OCF 3 -phenyl
CH 3
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
t-Bu
2-naphthalenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-r-Bu-phenyl
4-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
5-Me-2-pyridinyl
6-Me-2-pyridinyl '
WO 99/28305
PCT/US98/24265
54
Y
Column 1
Column 9
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
4-CFv2-pyridinyl
5-CF-5-?-nviHHiTiv1
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
6-CF^-2-pyridinyl
4 6-diMe-2-nvrirfinvl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
4-CF 3 -2-pyrimidinyl
h_I^ H l »_7_nunmiriiii\jl
u v.'i ^ -a i iimuixiy i
-CH=N-N(CH 3 )-
Z =
3-Me-phenyl
4-A/Tp-n V> *»n vl
-CH=N-N(CH 3 )-
Z =
3,5-diMe-phenyl
3-Cl-nhenvl
-CH=N-N(CH 3 )-
Z =
4-Cl-phenyl
3 5-diCl-nhenvl
-CH=N-N(CH 3 )-
Z =
3 -CF 3 -phenyl
4-f~ , T^-> -nhf*nv1
• a j ^jiighyj
-CH=N-N(CH 3 )-
Z =
3-OCF 3 -phenyl
-CH=N-N(CH 3 )-
Z =
2-naphthalenyl
4— /—Til i_r^Vi#»n\/l
-CH=N-N(CH,)-
z =
4-Me-2-ovridinvl
5-Me-2-pyridinyl
-CH=N-N(CH 3 )-
z =
6-Me-2-TYvridinv1
h - L. r ^ -J. -pynainy l
-CH=N-N(CH 3 )-
z =
5 -CFi -2-n vri din vl
o-^r^-x-pynainyi
-CH=N-N(CH,)-
z =
4 . 6-diMe-2-n vri H i nvl
4-CF3-2-pyrimidinyl
-CH 2 OC(SMe)=N-
z =
4-CF 3 -phenyl
j 2 pnenyi
-CH 2 OC(SMe)=N-
z =
4-OCF 3 -phenyl
j'ULrj -pnenyj
-CH 2 OC(SMe)=N-
z =
3-Cl-phenyl
-CH 2 OC(SMe)=N-
z =
3,5-diCl-phenyl
-CH 2 OC(SMe)=N-
z =
4-Me-phenyl
j uiivie-pnenyi
-CH 2 OC(SMe)=N-
z =
2-naphthalenyl
u lvie-^-pynuinyi
-CH 2 OC(SMe)=N-
z =
4-Me -2-pyridiny 1
-CH 2 OC(SMe)=N-
z =
5-CF-j-2-pvridinvl
S _ \^f»_v — TTV/nriinx/l
-CH 2 OC(=S)NMe-
z =
4-CF->-phenyl
3-CJF^-nhenvl
-CH 2 OC(=S)NMe-
z =
4-OCF 3 -phenyl
3-OCF3-phenyl
-CH 2 OC(=S)NMe-
z =
3-Cl-phenyl
4-C 1-pheny 1
-CH 2 OC(=S)NMe-
z =
3,5-diCl-phenyl
3-Me-phenyl
-CH 2 OC(=S)NMe-
z =
4-Me-phenyl
3 , 5-diMe-p.henyl
-CH 2 OC(=S)NMe-
z =
2-naphthalenyl
6-Me-2-n vri di n vl
-CH 2 OC(=S)NMe-
z =
4-Me-2-pyridinyl
4 6-diMe-2-nvridinv1
-CH 2 OC(=S)NMe-
z =
5-CF 3 -2-pyridinyl
5-Me-2-nvridinv1
-SCH 2 -
z =
2-Me-phenyl
2,5-diMe-phenyl
-SCH 2 -
z =
3-CF 3 -phenyl :
4-CF 3 -phenyl
-SCH 2 -
z =
4-Me-phenyl
4-f-Bu-phenyl
-SCH 2 -
z =
3-Cl-phenyl
4-Cl-phenyl
-SCH 2 -
z =
2-Me-5-Cl-phenyl
3-/-Bu-phenyl
-SCH 2 -
z =
2-naphthalenyl
1-naphthalenyl
-SCH 2 -
z =
3-pyridinyl
4-pyridinyl
WO 99/28305 PCT/US98/24265
55
Y
• Column 1
Pnlumn 9
-SCH 2 -
z =
6-Me-2 -py ridiny 1
S 7 Ji-tptrnlwrlrr* *>
j,u, / ,o Lcuaiiyui U"Z~
nonntn o 1 otit rl
lidpil iilalcil yl
-CH 2 0-N=C(SCH 3 >
z =
3-CF*5 -nhenvl
j "Ucr ^-pncny i
-CH 2 0-N=C(SCH 3 )-
z =
3-Me-nhenvI
H—k^r 3-pneny i
-CH 2 0-N=C(SCH 3 )-
z =
4-OCF 3 -phenyl
4-Me-phenyl
-CH 2 0-N=C(SCHi)-
z =
3-Cl-nhpnvl
jp-aiL-i-pnenyl
-CH 2 0-N=C(cyclopropyl)-
z =
3 -CF 3 -phenyl
j-uLr ^-pnenyi
-CH 2 0-N=C(cyclopropyl)-
z =
3-Me-phcnyl
^ Vw--T T -UIJCIl yl
-CH 2 0-N=C(cyclopropyl)-
z =
4-OCF 3 -phenyl
4-Me-phenyl
-CH 2 0-N=C(cyclopropyl)-
z =
3-Cl-phenyl
3,5-diCl-phenyl
Table 2c
= CF 3
Y
Column 1
Column 0
-O-
z =
Phenyl
^-(~VN4p-T>Wf*nvl
-O-
z =
4-CF-i-phenvl
j ivjv piiciiy i
-O-
z =
3-F-phenyl
-O-
z =
4-Me-phenyl
3-I-nhenvl
-O-
z =
3-SCH 3 -phenyl
2-Me-phenyl
-O-
z =
3-SCHF 2 -phenyl
4-SCH-j-nhenvl
-O-
z =
3-cyclohexyl-phenyl
4-SCHF 2 -phenyl
-O-
z =
6-CF 3 -2-pyridinyl
5-CF 3 -2-pyridinyl
-O-
z =
4-CF?-2-pyridinyl
6-Me-2-pyridinyl
-O-
z =
6-(CF 3 CHoO)-4-pyrimidinvl
5-Me-2-pyridinyl
-o-
z =
2-(CF 3 CH? 0)-4-pyrimidinyl
4-(CFiCH'>OV2-Dvrimidinvl
-o-
z =
4-Me-2-pyridinyl
3,5-diMe-phenyl
-o-
z =
2-naphthalenyl
5,6,7,8-tetrahydro-2-
naphthalenyl
-O-
z =
4-OCF 3 -phenyl
3-/-Bu-phenyI
-o-
z =
4-f-Bu-phenyl
6-(CF 3 CH 2 0)-2-pyrazinyl
-o-
z =
3-SCF 3 -phenyl
4-SCF 3 -phenyl
-o-
z =
4-CF 3 -6-Me-2-pyridinyl
3-CN-phenyl
-o-
z =
4,6-diMe-2-pyridinyl
3,5-di(CF 3 )-phenyl
-O-
z =
5-Cl-2-thiazolyl
5-1-2-thiazolyl
-o-
z =
5-OCF 3 -2-thiazolyl
5-(CH 3 ) 3 Si-2-thiazolyl
-o-
z =
5-CN-2-thiazolyl
5-SCH 3 -2-thiazolyl
WO 99/28305
PCT/US98/24265
56
Y
Column 1
Column 2
-O-
Z =
5-CF 3 -2-thiazoIyl
4-Me-5-Cl-2-thiazolyl
-O-
Z =
4-Me-5-I-2-thiazolyl
4-Me-5-CN-2-thiazolyl
-o-
Z =
4-Me-5-CF 3 -2-thiazolyl
-o-
Z =
3-(HCs=C)-phenyl
3-(CH 3 C=C)-phenyl
-o-
Z =
3-((CH 3 ) 3 CCsC)-phenyl
3-((CH 3 ) 3 SiCsC)-phenyl
-o-
Z =
3-([>-C=C>phenyl
5-Me-2-thienyl
-o-
z =
5-CCH-j ^ C-2-thienvl
-o-
z =
5-Br-2-thienyl
J> iiiiciiyi
-0-
z -
4-Me-2-th ipnvl
■ i»iv tu.1 vliy I
a /pit \ /-* 1
4-(Cti3)3C-2-thienyl
-o-
z =
4-Cl-2-thienvl
n-ur-z-tnienyi
-0-
z =
4-1-2-thienvl
4,D-aiivle-2-tiiienyl
-o-
z =
4-Me-5-13r-2-tnienyl
-o-
z =
4-Me-5-T-2-thienvl
j-Li-x-tnienyi
-o-
z =
5-Me-3-thienv1
j-C^-ri 3 J 3 t--j-tnienyl
-o-
z =
5-CI-3-thienvl
j-jsr-j-inienyi
-o-
z =
5-I-3-thienyl
/I A if a O Gianni
*r-ivie- j - inieny i
-o-
z =
4-fCHi^C-3-thienvl
**- l^i - j -inicny i
-o-
z -
4-Br-3-thienyl
"4— i- j-uiienyi
-o-
z =
4,5-diMe-3-thienyl
*r-iYie-j-^i-j-uiienyi
-o-
z =
4-Me-5-Br-3-thienyl
4-K/ff»_ ^ _ T- *l -tK i *»ri\/1
-o-
z =
2-Cl-3-thienyl
•t. v_-r "3 -pncny I
-CH 2 0-
z =
Phenyl
-j-v^r^-pncnyi
-CH 2 0-
z =
2-Me-5-z'-Pr-phenyl
*JJ\fia-A nPn<»
^-ivie-*t-ui_,xi3-pnenyi
-CH 2 0-
z =
4-OCF 3 -phenyl
x.-ivic-j-v^r T-piicnyi
-CH 2 0-
z =
3-OCHF 2 -phenyl
*t"\yviir o-piiciiyi
-CH 2 0-
z =
3.5-difCFiVnhenvl
z-ivie-H-^L^iir 2 - pnenyi
-CH 2 0-
z =
-2-nvridinvl
v# ^ — * A> pJrllUUlyl
•j-wi^r^-pnenyi
-CH 2 0-
z =
4 -C Pi - 2-n vri H i nvl
4-Mc-2 -pyndiny 1
-CH 2 0-
z =
5 -Me-2 -pyridiny 1
-CH 2 0-
z =
3,6-diMe-2-pyridinyl
S-CFi-^-Tivridinvl
v»».b. ■* ^> pjiiuuiyi
-CH 2 0-
z =
4,6-diMe-2-pyridinyl
6-OCF 3 -2-pyridinyl
-CH 2 0-
z =
4-CF 3 -6-Me-2-pyridinyl
3-Me-2-pyridinyl
-CH 2 0-
z =
4-Cl-2-pyrimidinyl
6-Me-2-pyridinyl
-CH 2 0-
z =
4-Cl-2-pyrimidinyl
3-Et-phenyl
-CH 2 0-
z =
2,6-diMe-4-pyridinyl
2,4,6-triMe-phenyl
-CH 2 0-
z =
3-Cl-2-pyridinyl
6-C1 -4-pyrimidiny 1
WO 99/28305
PCT/US98/24265
57
Y
Column 1
Column 2
-CH 2 0-
Z =
1-napthalenyl
£.j j,u~uiivj.c~piiciiyi
-CH 2 0-
Z =
6-Cl-2-pyrazinyl
4— — 7— nx/riTTiiriinxj'l
• v^i v ^ pyiiiiiiiiiiiy 1
-CH 2 0-
Z =
6-CF->-4-pvrimidinvl
7 — / - P r— n fi **n v 1
» iri - pucuyi
-CH 2 0-
Z =
3-Me-2-pyridinyl
4 - 1 - 9 »n vri H i -n \/1
~ v^i-z-pynuuiyi
-OCH 2 -
Z =
2-Me-phenyl
j-uiivie-pixenyi
-OCH 2 -
Z =
3 -CF 3 -phenyl
4-CFo -nhen vl
-OCH 2 -
Z =
4-Me-phenyl
*t~*-i5u-piicnyi
-OCH 2 -
Z-
3-Cl-Dhenvl
4-d-pnenyi
-OCH 2 -
z =
-w-iiu-pnenyl
-OCH 2 -
Z =
2-naphthalenyl
i -iidpncnaieny i
-OCH->-
z =
3 -n vri Hi iwl
4-pyridinyl
-OCH 2 -
z =
6-lvle-2 -d vri di n v 1
tetrahydro)naphthalenyl
-CH 2 0-N=C(CH 3 )-
z =
3-Me-phenyl
*+-*_r 3 -pnenyi
-CH 2 0-N=C(CH 3 )-
Z-
3.5-diMfi-nheTvvl
j-ci -pnenyi
-CH 2 0-N=C(CH 3 >
z =
4-Br-phenyl
^-Hi/'tf* s, P,»\ niton,,!
j,j-am^r3^-pnenyi
-CH 2 0-N=C(CH 3 )-
z =
4-OCHFo-Dhenvl
*T-/-r> u-pneny 1
-CH 2 0-N=C(CH 3 )-
z =
3-/-Bu-phenyl
•^■v^-T 3 -z-pyncnny 1
-CH 2 0-N=C(CH 3 )-
z =
4-OCF 3 -phenyl
-CH 2 0-N=C(CH 3 )-
z =
5-Me-2-pyridinyl
*t-v^.jr 3-D-ivie-z-pyriainyi
-CH 2 0-N=C(CH 3 )-
z =
4-Me-2-pyridinyl
\iiivic~i-pyriuuiyj
-CH 2 0-N=C(CH 3 )-
z =
6-Me -2 -ovridi n vl
6-CF3-2-pyndinyl
-CH 2 0-N=C(CH 3 }-
z =
6-OMe-2-pyridinyl
2. 6-diMe-4-Dvridin vl
-CH 2 0-N=C(CH 3 )-
z =
2,6-diCl-4-pyridinyl
w\^x^3 ^ pyiiuinyi
-CH 2 0-N=C(CH 3 )-
z =
4-OMe-2-pyridinyl
t-v^^-r 3 -x-p yriuinyi
-CH 2 0-N=C(CH 3 )-
z =
5-OCHF 2 -2-pyridinyl
w" WV/I 3 p V I lUllly 1
-CH 2 0-N=C(CH 3 )-
z =
4-OCHF 2 -pyridinyl
j 3 v_,ri2w ^pnenyi
-CH 2 0-N=C(CH 3 )-
z =
o-OCHFo-2-Dvridinvl
j'H i-pnenyi
-CH 2 0-N=C(CH 3 )-
z =
1 -naphthaleny I
1 ,z,^,4-tetranyaro-2-
nEphthalenyl
-CH 2 0-N=C(CH 3 )-
z =
3-SMe-phenyl
3-ethynylphenyl
-CH 2 0-N=C(CH 3 )-
z =
f-Bu
2-F-5-CF 3 -phenyl
-CH=N-OCH(CH 3 )-
z =
4-CF3-phenyl
3-CF 3 -phenyl
-CH=N-OCH(CH 3 )-
z =
4-OCF 3 -phenyl
3-OCF 3 -phenyl
-CH=N-OCH(CH 3 )-
z =
3-Cl-phenyl
4-Cl-phenyl
-CH=N-OCH(CH 3 )-
z =
3,5-diCl-phenyl
3,5-di(CF 3 )-phenyl
-CH=N-OCH(CH 3 )-
z =
3-Me-phenyi
4-Me-phenyl j
WO 99/28305
PCT/US98/24265
58
Y
Column 1
Column 2
-CH=N-OCH(CH 3 )-
Z =
2-naphthalenyl
4-OCHF->-i>henvl
-CH=N-OCH(CH 3 )-
Z =
3-OCHF 2 -phenyl
4-CF-* -2-rwriHinvl
-CH=N-OCH(CH 3 )-
Z =
5-CF 3 -2-pyridinyl
r\—{^ ™ v_tfV\/t"iiliwM/l
v vi "2 ^.~^jy l iLiiiiy i
-CH=N-OCH(CH 3 )-
Z =
4-Me-2-pyridinyl
5- Me-^-nvridinvl
-CH=N-OCH(CH 3 )-
Z =
6-Me-2-pyridinyl
4-CF-^ -fi-Mfi-^-twriHirivl
-CH=N-OCH(CH 3 )-
Z =
4-OCF 3 -2-pyridiny 1
S_Of~ , F«N_9_rv\rY-iHiMwl
^ r "3 -z-pynuinyi
-CH=N-OCH(CH 3 )-
Z =
6-OCF 3 -2-pyridinyl
4-OCHF*> -2-nvri d in vl
-CH=N-OCH(CH 3 )-
Z =
5-OCHF 2 -2-pyridinyl
o-v/^xxt2 pyncnnyi
-CH=N-OCH(CH 3 )-
Z =
3-/-Bu-phenyl
4-/-T-in-nhpnv1
-CH 2 -SC(Et)=N-
Z =
4-CF 3 -phenyl
j v pncnyi
-CH 2 -SC(Et)=N-
Z =
4-OCF 3 -phenyl
j'ubr "3 ~pjiciiyi
-CH 2 -SC(Et)=N-
Z =
3-Cl-phenyl
-CH 2 -SC(Et)=N-
Z =
3,5-diCl-phenyl
j, j-ui^^ro^-pnenyi
-CH 2 -SC(Et)=N-
Z =
3-Me-phenyl
4— Ayf p—n h on i/ 1
t ivic~ u iici l y i
-CH 2 -SC(Et)=N-
Z =
3,5-diMe-phenyl
* i iou 1 1 uim t? j i y i
-CH 2 -SC(Et)=N-
Z =
6-Me-2 -pyridinyl
t- ivie -z-py nuiny i
-CH 2 -SC(Et)=N-
Z =
4,6-diMe-2-pyridinyl
S-C^l-^-nvriHinvl
-CH 2 -SC(Et)=N-
Z =
4,6-diCl-2-pyridinyl
S— N^P— .V— twi-i/Hiym./I
j ivic~*"pyiiuinyi
-CH 2 -SC(Et)=N-
Z =
S-CF'j^-pyridinvl
5-Rr-fi-Mp-?-nvrirliTvvl
-CH 2 -SC(=S)NMe-
Z =
4-CF 3 -phenyl
^-f F*> -TlVlPTlvl
-CH 2 -SC(=S)NMe-
z =
4-OCF 3 -phenyl
3-OCF-> -nhenvl
-CH 2 -SC(=S)NMe-
z =
3-Cl-phenyl
4-Cl-phenyl
-CH 2 -SC(=S)NMe-
z =
3,5-diCl-phenyl
3 S-difCFil-nhenvl
-CH 2 -SC(=S)NMe-
z =
3-Me-phenyl
4-A4p-nhpnvl
-CH 2 -SC(=S)NMe-
z =
3,5-diMe-phenyl
^-nnnhthnlpTivl
uaLJiiiiia-iviiy i
-CH 2 -SC(=S)NMe-
z =
6-Me-2-pyridinyl
4-Mp-^-rwriHinvl
"T~AVXC <£r p^iiuxiiyi
-CH 2 -SC(=S)NMe-
z =
4,6-diMe-2-pyridinyl
5-Cl-2-nvridiTtvl
-CH 2 -SC(=S)NMe-
z =
4,6-diCl-2-pyridinyl
^-\4p-7 -nvri H i nv 1
-CH 2 -SC(=S)NMe-
z =
5-CF 3 -2-pyridinyl
-CH 2 SC(SMe)=N-
z =
3-Me-phenyl
4— N/t p—n h pti\r 1
^ ivic— piiciiy I |
-CH 2 SC(SMe)=N-
z =
3,5-diMe-phenyl
3-Cl-phenyl
-CH 2 SC(SMe)=N-
z =
4-Cl-phenyl
3,5-diCl-phenyl
-CH 2 SC(SMe)=N-
z =
3-CF 3 -phenyl
4-CF 3 -phenyl
-CH 2 SC(SMe)=N-
z =
3-OCF 3 -phenyl
4-OCF 3 -phenyl
-CH 2 SC(SMe)=N-
z =
3,5-di(CF 3 )-phenyl
CH 2 CH 2 -/-Bu
-CH 2 SC(SMe)=N-
z =
t-Bu
2-naphthalenyl
-CH 2 SC(SMe)=N-
z =
6-Me-2-pyridinyl
4-Me-2 -pyridinyl
WO 99/28305
PCT/US98/24265
59
■ Column 1
l^-uiuillll Z.
-CH 2 SC(SMe)=N-
Z =
4,6-diMe-2-pyridinyl
j i- *"pynuiny i
-CH 2 SC(SMe)=N-
Z =
4, 6-diCl-2-pyridinyl
j -ivic-^-py nainy i
-CH 2 SC(SMe)=N-
Z =
5-CF 3 -2-pyridinyl
j iJi vJ~lvic Z."Uyi lUlIly 1
-CH 2 S-
Z =
J-Cr3-pnenyl
-CH 2 S-
z =
z,5-aiMe-pnenyl
-CH 2 S-
z =
2-Et-nhenvl
j i-pneny i
-CH 2 S-
z =
2-d-nhpTivl
z,5-aiCl-pnenyl
-CH 2 S-
Z -
*t,u uuvic-x-pyr llLlKJlilyl
4-Me- 1 ,2,4-tnazol-3-yl
-CH 2 S-
z =
2-nanhthfllpnvl
1 -Me-2-imidazolyl
-CH 2 S-
z =
i t-ivic--t-py i uin amy i
5-Me-l,3,4-thiadiazol-2-yl
-CH 2 0-N=C(CH,)CH-.S-
z =
IVrt p— nnAm/l
■j lYic-pnenyi
2-Me-phenyl
-CH 2 0-N=C(CH^)CH?S-
z =
j r 3 -pneny j
4-CF 3 -phenyl
-CH 2 0-N=C(CHi)CHoS-
z =
d -v^i-pncnyi
2-Et-phenyl
-CH 2 0-N=C(CH*)CH->S-
z -
4-P1 nfiftn^;l
2-naphthalenyl
-CH 2 0-N=C(CH 3 )CH,S-
z =
2 S-Hilvf P-T\lipn\/1
uuvic piicxly I
4-C r 3 -2-pyndrny I
-CH 2 0-N=C(CH,)CH 7 0-
z =
-7 i»mc— puciiyi
2-Me-phenyl
-CH 2 0-N=C(CH-j)CH?0-
z =
4 — \/Tf _f*V» A1Y\ / 1
*t~ivic-piiciiyi
3-CF 3 -phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4- CF -» -nhpn vl
4-u-pnenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
3-Cl-Dhenvl
3,5-diMe-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
2.5-diMe-nhenvl
z-me-D-i-rr-pnenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
3 -E t-pheny 1
6-CF 3 -2-p3^ridinyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4-CF-a-2-Dvridinvl
j ^* 3 -z-pynainyi
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
6-Me-2-pyridinyl
iv-iv - A~pyiiuiiiy i
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4-\^f p-2-nvri H j n vl
i -napnuiaienyi
-CH 2 O-N=C(CH 3 )CH 2 0-
z =
2-naDhthalenvl
2-CF^ -phenyl
-CH 2 CH 2 -
z =
2-M e-nhen vl
2,5-diMe-phenyl
-CH 2 CH 2 -
z =
3-CF-5 -nhenvl
n-Lr 3 -pnenyj
-CH 2 CH 2 -
z =
3-Cl-phenyl
i-piiciiy i
-CH 2 CH 2 -
z =
3-OCFo -nhenvl
^-^Jur^-pnenyl
-CH 2 CH 2 -
z =
2-Et-nhetivl
ji-xvie-D-ci-pnenyl
-CH 2 CH 2 -
z =
2-naphthalenyI
3,6"diMe-2-pyridinyl
-CH=C(CH 3 )-
z =
3-Me-phenyl
4-Me-phenyl
-CH=C(CH 3 )-
z =
3,5-diMe-phenyl
3-Cl-phenyl
-CH=C(CH 3 )-
z =
4-Cl-phenyl
3-OCF 3 -phenyl
-CH=C(CH 3 )-
z =
4-OCF 3 -phenyl
3 -CF3 -phenyl
-CH=C(CH 3 )-
z =
4-CF 3 -phenyl
2-naphthalenyl
-CH=C(CH 3 )-
z =
4-CF 3 -2-pyridinyl
6-CF3 -2-pyridinyl
WO 99/28305
PCT7US98/24265
60
Y
Column 1
column 2
-CH=N-N=C(CH-i)-
z =
4-Me-phenyl
-CH=N-N=C(CH'j)-
2 =
j 2 pnenyi
4-CF3 -phenyl
-CH=N-N=C(CH3)-
7 =
j -wLr ^ -p nenyi
4-OCF3-phenyl
-CH=N-N=Cf CH-j V
7 _
3,5-diMe-phenyl
3-Cl-phenyl
-CH=N-N=CfCHiV
7 _
^-ci-pnenyi
3,5-diCl-phenyl
-CH=N-N=CfCH^V
^■tr 3-z-pynainyI
5 -CF 3 -2-pyridinyl
-CH=N-N=CfCHiV
7 —
6-CF3~2-pyridinyl
4-Me-2-pyridinyl
-CH=N-N=CfCH^-
7 i
5 -Me-2 -pyridiny 1
6-Me-2-pyridiny]
-CH=N-N=C(CH3>-
7 —
2-naphthal eny 1
4,6-diMe-2-pyridinyl
-CH=N-N=CCCH-. V
i-fct-pnenyl
r-Bu
-CH?0-N=C(CH^Cf=NOCH-»V
7 =
3-Me-phenyl
4-Me-phenyl
-CHoO-N=CrCH^^Cf=NOrH^V
7 —
j,3-diMe-pnenyl
3-Cl-phenyl
-CHoO-N=C(CH^C(=NOCH->V
7 —
*t-ci-pnenyl
3,5-diCl-phenyl
-CHoO-N=C(CH^C(=NOCH-»V
7 —
O /~ , tr_ . ,1
j-^r3-pnenyi
4-CF3 -phenyl
-CH?0-N=C(CHi)Cr=NOCH:>V
7 —
j ,j -ai(C.r 3 )-pnenyl
3-OCF 3 -phenyl
-CH 2 0-N=C(CHo)Cf=NOCH^V
2 =
*t u v r 3-pnenyi
CH 3
-CH?0-N=C(CH^)C(=NOCH? V
7 —
l-DU
2-naphthalenyl
-CHoO-N=C(CH^')C(=NOCHo
2 —
-ou-pneny 1
4-Me-2-pyridinyl
-CH 2 O-N=C(CH:0C(=NOCH-> V
2 =
5-Me-2-pyndinyl
6-Me-2-pyridinyl
-CH 2 0-N=C(CH^)C(=NOCHoV
2 =
" \-*r 3 -z-pynainyi
5-CF3-2-pyndinyl
-CH 2 0-N=C(CHo)C(=NOCHn )-
z =
u- v^x^ 3 -z-pynainyi
4,o-diMe-2-pyndinyl
-CH 2 0-N=C(CHi)C(=NOCH?y
2 =
w r 3 - z -pyrmii a my 1
6-CF 3 -2-pyrimidinyl
-CH=N-N(CH?)-
2 =
4-Me-phenyl
-CH=N-N(CH?)-
z =
^ S— H i\zTf»-'nV»f»r»\/1
J-Cl-pnenyJ
-CH=N-N(CHi)-
z =
4-C1 -r»h**nvl
3,5-aid-pnenyl
-CH=N-N(CHn)-
z =
j ~pncny 1
4-CF3-phenyl
-CH=N-N(CH*)-
2 -
j"ucri -p nenyi
4-OCF3 -phenyl
-CH=N-N(CH 3 )-
2 =
z-iiapo.uiai6n.yi
4-/-Bu-phenyl
-CH=N-N{CH3>-
7 —
4-Me-2 -pyridiny 1
5-Me-2-pyridinyl
-CH=N-NfCH-jV
7 —
6-Me-2 -pyridiny I
4-CF3-2-pyridinyl
-CH=N-N(CH 3 )-
Z =
5-CF3 -2-pyridiny I
u~v_yX 3 pynuiny i
-CH=N-N(CH 3 )-
z =
4,6-diMe-2-pyridinyl
4-CF 3 -2-pyrimidinyl
-CH 2 OC(SMe)=N-
z =
4-CF 3 -phenyl
3-CF3-phenyl
-CH 2 OC(SMe)=N-
z =
4-OCF3-phenyl
3-OCF 3 -phenyl
-CH 2 OC(SMe)=N-
z =
3-Cl-phenyl
4-Cl-phenyl
-CH 2 OC(SMe)=N-
z =
3,5-diCl-phenyl
3-Me-phenyl
-CH 2 0C(SMe)=N-
z =
4-Me-phenyl
3,5-diMe-phenyl
WO 99/28305
PCT/US98/24265
61
Y
Column 1
Column 2
-CH 2 OC(SMe)=N-
z =
2-nanhthalenvl
6-Me-2-pyridinyl
-CH 2 OC(SMe)=N-
z =
4-Me-2-fwririinv1
4,6-diMe-2-pyridinyl
-CH 2 OC(SMe)=N-
z =
i ^> JJYllUUiyi
5-Me-2-pyridinyl
-CH 2 OC(=S)NMe-
z =
d-PF^-nhpnvl
3-CF 3 -phenyl
-CH 2 OC(=S)NMe-
z =
4-OCFi-Dhenvl
3-OCF 3 -phenyl
-CH 2 OC(=S)NMe-
z =
3-Cl-nhenvl
4-Cl-phenyl
-CH 2 OC(=S)NMe-
z =
3 5-diCl-Dhenvl
3-Me-phenyl
-CH 2 OC(=S)NMe-
z =
3,5-diMe-phenyl
-CH 2 OC(=S)NMe-
z =
nantithalpTivl
6-Me-2-pyridinyl
-CH 2 OC(=S)NMe-
Z -
4— K/fp— ~T>V7f""iHin\/l
4,6-diMe-2-pyridinyl
-CH 2 OC(=S)NMe-
z =
j — C* P -> - 0 — t\\it\ H i rwA
v^i ^ ^"^jyiiuuiyi
5-Me-2-pyridinyl
-SCH 2 -
z =
9-N/lp_r>Hf»n\/1
2,5-diMe-phenyl
-SCH 2 -
z =
S-CF^-phenyl
4-CF 3 -phenyl
-SCH 2 -
z =
4-]VTe-nhf > nvl
4-r-Bu-phenyl
-SCH?-
z =
3-Cl-nhenvl
4-Cl-phenyl
-SCH->-
z =
3-f-Bu-phenyl
-SCH 2 -
z =
2 — n a ri VitK n 1 #* ri\/1
x xiajjiiLiiaiCIlYl
1-naphthalenyl
-SCH 2 -
z =
l-nvnninul
4-pyridinyl
-SCH 2 -
z =
6— N/fp-9— nvri Hinvl
™ -^«v ^ y i luiily l
5,6,7,8-tetrahydro-2-
naphthalenyl
-CH 2 0-N=C(SCtti)-
z =
T_ l^F -» .nnpnvl
3-OCF 3 -phenyl
-CH 2 0-N=C(SCH 3 )-
z =
\ _ .nh A*T* 1 1
j ~ivic "pncny i
4-CF 3 -phenyl
-CH 2 ON=C(SCH 3 )-
z =
4-OCF 3 -phenyl
4-Me-phenyl
-CH20-N=C(SCH3)-
z =
3-Cl-phenyl
3,5-diCl-phenyl
\_*n.2^-'-iN— i^cyciopropyij-
z =
3-CF 3 -phenyl
3-OCF 3 -phenyl
^n2*- , -iN— ^cyciopropyi^-
z =
3-Me-phenyl
4-CF 3 -phenyl
^HoO-N^wclopropvl)-
z =
-nhpnvl
4-Me-phenyl
-CH 2 0-N=C(cyclopropyl)-
z =
- ' v_, i-^j iiciiy i
3,5-diCl-phenyl
Table 3a
= CH 3
Y
Column 1
Column 2
-O-
z =
Phenyl
3-OMe-phenyl
-O-
z =
4-CF 3 -phenyl
3-Me-phenyl
-O-
z =
3-F-phenyl
3-OCF 3 -phenyl
-O-
z =
4-Me-phenyl .•'
3-I-phenyl
-O-
z =
3-SCH 3 -phenyl
2-Me-phenyl
WO 99/28305
PCT/US98/24265
62
Y
Column 1
Column 2
-O-
z =
3-SCHF 2 -phenyl
4-SCH'5-nhenvl
-O-
z =
3 -cyclohexyl-phenyl
4-SCHF 2 -phenyl
-O-
z =
6-CF3-2-pyridiny]
5-CFn -2-Dvridinvl
-O-
z =
4-CF3-2-pyridinyl
6-Me-2 -n vri di nv 1
-O-
z =
6-(CF 3 CH 2 0)-4-pyrimidinyl
5-Me-2-pyridinyl
-O-
z =
2-(CF3CH 2 0)-4-pyrimidinyl
4-CCF7CH'>0'>-2-t)vrimidinvl
-O-
z =
4-Me-2-pyridinyI
j|j uuvic uiicijyi
-O-
z =
2-naphthalenyl
5 6 7 8-tetrahvdro-?-
nanhth a 1 envl
-O-
z =
4-OCF 3 -phenyl
3 -/-B u-nh en vl
-O-
z =
4-f-Bu-phenyl
O— T C K ^ C^H^ 0^-2 -nvrn ■yin \/l
-o-
z =
3-SCF 3 -phenyl
-o-
z =
4-CF3-6-Me-2-pyridinyl
-o-
z =
4,6-diMe-2-pyridinyl
-o-
z =
5-Cl-2-thiazolyl
5-I-2-thiazolv!
-o-
z =
5-OCF3-2-thiazolyl
-o-
z =
5-CN-2-thiazolyl
5-SCH3-2-thiazolyl
-0-
z =
5-CF3-2-thiazolyl
4-Me-5-Cl-2-thiazolyl
-o-
z =
4-Me-5-I-2-thiazolyl
4-Me-5-CN-2-thiazolyl
-0-
z =
4-Me-5-CF 3 -2-thiazolyl
-o-
z =
3-(HC=C)-phenyl
3-(CH 3 CsC)-phenyl
-o-
z =
3-((CH 3 ) 3 CCsC)-phenyl
3-((CH 3 ) 3 SiC=C)-phenyl
-o-
z =
3-( £>— C==C>phenyl
5-Me-2-thienyl
-o-
z =
5-(CH 3 ) 3 C-2-thienyl
5-Cl-2-thienyl
-o-
z =
5-Br-2-thienyl
5-I-2-thienyl
-o-
z =
4-Me-2-thienyl
4-(CHi)oC-2-thienvl
-o-
z =
4-Cl-2-thienyl
4-Br-2-thienyl
-o-
z =
4-I-2-thienyl
4 5-diMe-2-thienvl
-o-
z =
4-Me-S-Cl-2-thienyl
4-Me-5-Br-2-thienvl
* x»xv — ' j— 'i ^ uuwiiy 1
-0-
z =
4-Me-5-I-2-thienyl
3-Cl-2-thienyl
-0-
z =
5-Me-3-thienyl
5-(CH 3 ) 3 C-3-thienyl
-O-
z =
5-Cl-3-thienyl
5-Br-3-thienyl
-o-
z =
5-I-3-thienyl
4-Me-3-thienyl
-o-
z =
4-(CH 3 ) 3 C-3-thienyl
4-Cl-3-thienyl
-0-
z =
4-Br-3-thienyl
4-I-3-thienyl
-o-
z =
4,5-diMe-3-thienyl
4-Me-5-Cl-3-thienyl
WO 99/28305
PCT/US98/24265
63
Y
Column 1
Column 2
-O-
Z =
4-Me-5-Br-3-thienyl
4-Me-5-I-3-thienyl
-O-
Z =
2-Cl-3-thienyl
2-CF 3 -phenyl
-CH 2 0-
Z =
Phenyl
S-CF^-nhenvl
-CH 2 0-
Z =
2-Me-5-/-Pr-phenyl
2-Me-4-OCHi -nhenvl
-CH 2 0-
Z =
4-OCF 3 -phenyl
2-Me-5-CF-j -nhenvl
-CH 2 0-
Z =
3-OCHF 2 -phenyl
4-OCHF 2 -phenyl
-CH 2 0-
Z =
3,5-di(CF 3 )-phenyl
2-Me-4-OCHF->-nhenvl
-CH 2 0-
Z =
6-CF 3 -2-pyridinyl
3-OCF->-Dhenvl
-CH 2 0-
Z =
4-CF 3 -2-pyridinyl
4-Me-2-nvrtHinv1
-CH 2 0-
Z =
2-Me-4-OCF 3 -phenyl
S — \/f f -9-r\vriH in vl
J i ^JjrllUUljl
-CH 2 0-
Z =
3,6-dIMe-2-pyridinyl
^ - f P -» - 7 — n vri /I i n \/l
-CH 2 0-
Z =
4,6-diMe-2-pyridinyl
-CH 2 0-
Z =
4-CF 3 -6-Me-2-pyridinyl
^-Mp- 9 -TYVt*i H i nvl
j ivit. z, jj^ i luiiiy i
-CH 2 0-
Z =
4-Cl-2-pyrimidinyl
f\— A/ff -'5— TivriH in\/1
-CH 2 0-
Z =
4-Cl-2-pyriniidinyl
T*f— ■nhpfivl
•J j_> i~ L/iiciiy l
-CH 2 0-
*•
Z =
2,6-diMe-4-pyridinyl
^ s i T ) u*-Liiivit;~piit;nyi
-CH 2 0-
Z =
3-Cl-2-pyridinyl
6-C I -4 -twri m i fi in vl
-CH 2 0-
Z =
1-napthalenyl
-» j V/ U UYAC JJ11G1IY 1
-CH 2 0-
z =
6-Cl-2-pyrazinyl
nvriTniHfrivl
■ vi i ^jyi iiiiiumy J
-CH 2 0-
z =
6-CF 3 -4-pyrimidinyl
2-z-Pr-ohenvl
-CH 2 0-
z =
3-Me-2-pyridinyl
4-Cl-2-pyridinyl
-OCH 2 -
z =
2-Me-phenyl
2,5-diMe-phenyl
-OCH 2 -
z =
3-CF 3 -phenyl
4-CF 3 -phenyl
-OCH 2 -
z =
4-Me-phenyl
4-f-Bu-phenyl
-OCH 2 -
z =
3-Cl-phenyl
4-Cl-ohenvl
-OCH 2 -
z =
2-Me-5-Cl-phenyl
3 -/-B u-nhenvl
-OCH 2 -
z =
2-naphthalenyl
1 -naphthalenyl
-OCH 2 -
z =
3-pyridinyl
4-nvriHinvl
-OCH 2 -
z =
6-Me-2-pyridinyl
2-C5 6 7 8-
icuaiiy uiuiiiajjjiuiaicnyi
-CH 2 0-N=C(CH 3 )-
z =
3-Me-phenyl
4-CF 3 -phenyl
-CH 2 0-N=C(CH 3 )-
z =
3,5-diMe-phenyl
3-Cl-phenyl
-CH 2 0-N=C(CH 3 )-
Z-
4-Br-phenyl
3,5-di(CF 3 )-phenyl
-CH 2 0-N=C(CH 3 )-
Z =
4-OCHF 2 -phenyl
4-NBu-phenyl
-CH 2 0-N=C(CH 3 )-
Z =
3-MJu-phenyl
5-CF 3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )-
z =
4-OCF 3 -phenyl
3-OCHF 2 -phenyl
-CH 2 0-N=C(CH 3 >
z =
5-Me-2-pyridinyl
4-CF 3 -6-Me-2-pyridinyl
WO 99/28305
PCT/US98/24265
64
Y
Column 1
Column 7
-CH 2 0-N=C(CH 3 )-
Z =
4-Me-2-pyridinyl
• j vj uuviv a« ^ijfi luuiy 1
-CH 2 0-N=C(CH 3 )-
7 =
6-Me-2-pyridinyl
2 z-pynairiyi
-CH 2 0-N=C(CH 3 )-
Z =
6-OMe-2-pyridinyl
2,6-diMe-4-pyridinyl
-CH 2 0-N=C(CH 3 )-
Z =
2,6-diCl-4-pyridinyl
5_Of" , F-*_9_n\/riHin\/1
v\zf 3 -A-|jyi lumy 1
-CH 2 0-N=C(CH 3 )-
Z =
4-OMe-2-Dvridinvl
4 HPT?* 1 rvim^mrl
H-VJL/r 3-Z-pyriuinyl
-CH 2 0-N=C(CH 3 )-
Z =
5-OCHF2 "2-pyridinyl
6-OC -2 -pyndiny I
-CH 2 0-N=C(CH 3 )-
Z =
4-OCHFo-ovridinvI
j"vwr 3 ri2<J jpnenyl
-CH 2 0-N=C(CH 3 )-
Z =
^OCHFT-2-nvridiTivl
3-Et-phenyl
-CH 2 0-N=C(CH 3 )-
z =
1 -nanhthalenvl
1 ,2, i ,4-tetranyaro-2-
napninai eny i
-CH 2 0-N=C(CH 3 )-
Z =
»j 1 vie ** u 1 1 Cj 1 y i
3-ethynylphenyl
-CH 2 0-N=C(CH 3 )-
z =
/-Bu
z-r -D-L-i* 3 -pnenyi
-CH=N-OCH(CH-j)-
z =
4-CF->-nhenvl
3-cr3-pnenyi
-CH=N-OCH(CH 3 )-
z =
4-OCF-) -nhpTivl
j-Utr 3 -phenyl
-CH=N-OCH(CHh)-
z =
3-Cl-rihenvl
4-ci-piienyi
-CH=N-OCH(CH 3 )-
z =
3,5-diCl-phenyl
j,*?~ui^v^x'3J pnenyi
-CH=N-OCH(CH 3 )-
z =
3-Me-phenyl
t-ivic-pueny 1
-CH=N-OCH(CH 3 )-
z =
2-naphthalenyl
t-uLnr 2 "pnenyi
-CH=N-OCH(CH 3 )-
z =
3-OCHF 2 -phenyl
3 -z-pynoinyj
-CH=N-OCH(CH*)-
z =
5-CFi -2-nvridinvl
o-\_r3-z-pynainyl
-CH=N-OCH(CH 3 )-
z =
4-Me-2-pyridinyl
^» ^rt f rwrmntrv\ it
j ■ivic~^-pyriciiiiy 1
-CH=N-OCH(CH 3 >
z =
6-Me-2-pyridinyl
*t- v^r 3 -u-ivic-i-pyriainyi
-CH=N-OCH(CH 3 )-
z =
4-OCF 3 -2-pyridinyl
j - 3-z-pynuiny 1
-CH=N-OCH(CH 3 )-
z =
6-OCF 3 -2-pyridinyl
-CH=N-OCH(CH 3 )-
z =
5-OCHF->-2-Dvridinvl
6-OCHF2"2-pyridinyl
-CH=N-OCH(CH 3 )-
z =
3-f-Bu-phenyl
*T-i— DU~UI1CI1Y1
-CH 2 -SC(Et)=N-
z =
4-CFi -nhenvl
j-v^r 3-pncnyi
-CH 2 -SC(Et)=N-
z =
4-OCFi-Dhenvl
j-ui^r3-pnenyi
-CH 2 -SC(Et)=N-
z =
3-Cl-phenyl
4- C 1 -phenyl
-CH 2 -SC(Et)=N-
z =
3.5-diCl-nhenvl
j,D-ai^cr3^-pnenyi
-CH 2 -SC(Et)=N-
z =
3 -Me-phenyl
*»-ivie -pneny 1
-CH 2 -SC(Et)=N-
z =
3,5-diMe-phenyl
2-naphthalenyl
-CH 2 -SC(Et)=N-
z =
6-Me-2-pyridinyl
4-Me-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
4,6-diMe-2-pyridinyl
5-Cl-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
4,6-diCl-2-pyridinyl
5-Me-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
5-CF 3 -2-pyridinyl
5-Br-6-Me-2-pyridinyI
-CH 2 -SC(=S)NMe-
z =
4-CF 3 -phenyl
3-CF 3 -phenyl
WO 99/28305
PCT/US98/24265
65
Y
Column 1
v^oiuimx A
-CH 2 -SC(=S)NMe-
z =
4-OCFo-ohenvl
j-\J\^r 3-pnenyi
-CH 2 -SC(=S)NMe-
z =
3-Cl-ohenv!
f-^i-pnenyi
-CH 2 -SC(=S)NMe-
Z =
3 5-did-nhpfivl
j,D-ai(Ur 3 j-pnenyl
-CH 2 -SC(=S)NMe-
z =
j ivic~piiciiyi
4-Me-phenyl
-CH 2 -SC(=S)NMe-
z =
-\ Saninjfp.nnpmrl
jyj uii vic*pi icily i
2-naphthalenyl
-CH 2 -SC(=S)NMe-
Z -
- \/f P -. 9 _TW/i*i H i tlx/ 1
u - ivic -z.-py nuiny i
4-Me-2-pyridinyl
-CH 2 -SC(=S)NMe-
z =
4 fi— HilMf*-'?-TwriHiTivf1
~)« uiivic i.~pyiiuiiiyi
j-CI-2-pyndinyl
-CH 2 -SC(=S)NMe-
z =
*r,u uiv^i-^-pynuinyi
5-Me-2-pyridinyl
-CH 2 -SC(=S)NMe-
z =
j t z. pyi lLiiiiyi
5-Br-o-Me-2-pynduiyl
-CH 2 SC(SMe)=N-
z =
^— A^p—nhpnx/1
j ivxc uiiciiy i
4-Me-phenyl
-CH 2 SC(SMe)=N-
2 -
j**uuvic-pn.6nyi
3-Cl-phenyl
-CH 2 SC(SMe)=N-
z =
-pneny i
3,5-diCl-phenyl
-CH 2 SC(SMe)=N-
z =
A — f 1 Ih" >• _nn^ni./1
V-'X piicnyi
4-CF3-pnenyl
-CH 2 SC(SMe)=N-
Z =
4-(JCr3-pnenyl
-CH 2 SC(SMe)=N-
Z =
3.5-difCFil-Dhenvl
pT_f _/^tJ^ / TV,.
\^xi2^"2 ~
-CH 2 SC(SMe)=N-
Z =
f-Bu
z-napnuiaienyi
-CH 2 SC(SMe)=N-
z =
6-A/fe— ^-iwriHiiwl
v/ iTis L/y i iuiiiy i
4-Me-2 -pyridiny 1
-CH 2 SC(SMe)=N-
z =
4.6-diMe-2-ovridinvl
5"Cl-2-pyndinyl
-CH 2 SC(SMe)=N-
z =
4.6-diCl-2-nvridinv1
j -ivie-z-pynaiiiy 1
-CH 2 SC(SMe)=N-
z =
5 "CFj -2-pyridinyl
j~xji~vMviC"i~pyriQinyi
-CH 2 S-
z =
2 -Mp-nh f*n vl
j-tr 3 -pneny l
-CH 2 S-
z =
4~r^P^ .nlipnvl
•»"v^x "z*piicuyi
2,5-aiMe-pnenyl
-CH 2 S-
z =
2-Et-T>henv1
j-\^i-pnenyi
-CH 2 S-
z =
2-Pl-nhpnvl
2 t 5-aiCl-pnenyi
-CH 2 S-
z =
4 o— di RnP— ^wTivritniHitM/l
ijV/ uiivi^^^^pyx LLlllUUiyi
4-Me- 1 ,<J,4-tnazol-3-yl
-CH 2 S-
z =
2-n an h th a 1 pnvl
1 -Me-2-imidazolyl
-CH 2 S-
z =
4— NAp— "7— nvtnnni/4itnx/1
• ivA^-^-^/y i UillLUIiy 1
5-Me- 1 ,3 ,4-thiadiazol-2-yl
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
3-Vfe-nhpnvl
2-Me-phenyl
-CH 2 0-N=C(CH,)CH?S-
z =
4-Cr 3 -pnenyl
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
^-Pl-TlVlPTlvl
-J i pjiciiy i
2-tt-phenyl
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
4-Cl-phenyl
2-naphthalenyl
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
2,5-diMe-phenyI
4-CF 3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
3-Me-phenyI
2-Me-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4-Me-phenyl
3-CF 3 -phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4-CF 3 -phenyl
4-Cl-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
3-Cl-phenyl
3,5-diMe-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
2,5-diMe-phenyl
2-Me-5-/-Pr-phenyl
WO 99/28305
PCT/US98/24265
66
Y
Column 1
vuimiin J.
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
3-Et-ohenvl
6-CF3 -2-pyndinyl
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
4— CF*»-2-TWrifIinvl
~ V-'X < .*» ^yiLUlliyi
-2-pyndiny 1
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
6-Me-2-t>vridinvl
5 -1VIC"2 -pyridiny 1
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4"\le-2-r>vriHinv1
* J_> J » 1UU1Y 1
1 -ndpniiiaiciiyi
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
2-nanhthalf*TivI
2-CF^ -phenyl
-CH9CH9-
Z =
^-lvTp-nhpnvl
1VJ.C JJIIdxyi
z,3-aLivic-pnenyi
-CH 2 CH 2 -
x Z
z =
^— {~*F"> -r\hpnvl
vx j pucuyi
4-Cr3-pnenyl
-CH2CH9-
z =
3-Cl-nhenvl
H-vi-pnenyi
-CH 2 CH 2 -
z z
z =
3-OCF-> -nhenvl
4- Livr 3 -pnenyi
-CH9CH9-
z =
2-Et-nhfM"iv1
JL#4 x/xxvsxx y 1
z -ivie - d - vi-pneny 1
-CH 2 CH 2 -
X z
z =
2-nanhthalpnvl
j,o-aiiVie-z-pynainyl
-CH=C(CH 3 )-
z =
j xvx c-piicuy 1
4-Me-phenyl
-CH=C(CH^)-
z =
-'»•-' uiivxe pnenyi
j-vl-pnenyl
-CH=C(CH 3 )-
z =
4-Cl-nhenvl
■ vi pixviiy 1
3-ui r 3-pnenyl
-CH=C(CHo)-
z =
^-v , vi^3-piienyi
3-Or 3 -phenyl
-CH=C(CHa>
z =
4-r^F<* .nliAnAfl
~ vx j pnenyi
2-naphthalenyl
-CH=C(CH 3 )-
z =
4— f^F** — ^-r*\/T*iHin\/l
« vx ^ x pynuniyi
0- L-r 3 -l -pyndinyl
-CH=N-N=C(CH 3 )-
z =
3 -IVTe-nhpTivl
1UV LJXXV'XXy X
4-Me-phenyl
-CH=N-N=C(CH 3 )-
z =
3 - f"!F -» -oh pn vi
•H-vr3-pnenyi
-CH=N-N=C(CH 3 )-
z =
3-OPF'5 -nhenvl
v — x ^ LinciAyl
3 -pnenyi
-CH=N-N=C(CH 3 )-
z -
j» j unvxc-piieiiyi
j-Cl-pnenyl
-CH=N-N=C(CHo)-
z =
4-Cl-nhpnvl
j,j-oiL.i-pnenyi
-CH=N-N=C(CH^)-
z =
4— 1 Fi — n\7ririiTix/l
• vi t z.-py 1 iviiiiy i
D -Lr 3 -z-pyntlinyl
-CH=N-N=C(CHo)-
z -
n-\ F *^ — V— nvmHirn/l
v vi x. py 1 1 LI lily 1
4-Me-2-pyridinyl
-CH=N-N=C(CH 3 )-
z =
5-lVfe-2-TivriHiiiv1
6-Me-2-pyndinyl
-CH=N-N=C(CH 3 )-
z-
2-naohthalenvl
^,o-auvie-z-pynainyi
-CH=N-N=C(CHo)-
z =
3— Ft— nfipnvl
— ' x_» l ijxiciiy j
f-tJU
-CH 2 0-N=C(CH 3 )C(=NOCH,)-
z =
3-lVfe-r>Hf*rivl
i»iv ijxxvxi y i
4-Me-phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH-,)-
z =
-j j *^~un vxc~p iiciiy 1
j-vi -pnenyi
-CH 2 0-N=C(CH 3 )C(=NOCH^)-
z =
4— — Tih pm; 1
• vi - uiiciiy 1
3,3-aivl-phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
3-CF 3 -phenyl
4-CFi -nhenvl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
3,5-di(CF 3 >phenyl
3-OCF 3 -phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-OCF 3 -phenyl
CH 3
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
/-Bu
2-naphthalenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-/-Bu-phenyl
4-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
5-Me-2-pyridinyl
6-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-CF 3 -2-pyridinyl
5-CF 3 -2-pyridiny]
WO 99/28305
PCT/US98/24265
67
Y
Column 1
Column 2
CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
6-CF"i-2-pyridinyl
4 6-diMe-2-nvrirfinvl
CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
4-CF3 -2-pyrimidinyl
v V-^I "^ ^- ^J_yi lLiiiLiiityi
-CH=N-N(CHo)-
Z =
3-Me-phenyl
4- \/f r*— t^Vi r*ti\/l
-CH=N-N(CH 3 )-
Z =
3 , 5 -diMe-pheny 1
3-Cl-nhenvI
-CH=N-N(CH 3 )-
Z =
4-Cl-phenyl
3 5-diCl-nhenvl
-CH=N-N(CH 3 )-
Z =
3-CF3 -phenyl
4-CF-»-nhenv1
-CH=N-N(CH 3 )-
z =
3-OCF3-phenyl
-CH=N-N(CH 3 )-
z =
2-naphthalenyI
zl _ /_ R 1 1 _T\ Vl <»« \ / 1
- ij u-piicny 1
-CH=N-N(CH 3 )-
z =
4— \fe-2-nvridinvl
■ a u y 1 luui y 1
5-Me-2-pyndinyl
-CH=N-N(CH?)-
Z-
6-lVfe- 2-nvT*i H i n vl
^-^i^-z-pyncunyi
-CH=N-N(CH 3 )-
Z-
5-CF^ -2-nvrifiinvl
6-CF3 -2-pyndiny 1
-CH=N-N(CHi)-
z =
4 6-diMe-2~rwridmvl
4-CF3 -2-pyrimidinyl
-CH 2 OC(SMe)=N-
z =
4-CFi-t)henvl
3-CF3 -phenyl
-CH 2 OC(SMe)=N-
z =
4-OCF^-nhenvl
3 -pnenyi
-CH 2 OC(SMe)=N-
z =
3-Cl-phenyl
*t - 1 JJ1 icily 1
-CH 2 OC(SMe)=N-
z =
3,5-diCl-phenyl
j ivic — u u ciiy 1
-CH 2 OC(SMe)=N-
z =
4-Me-ohenvl
j, j -uuvie -pnenyi
-CH 2 OC(SMe)=N-
z =
2-naphthalenyl
D-ivic-x -pynciiny 1
-CH 2 OC(SMe)=N-
z =
4-Me-2-pyridinyl
*♦ , o-uuvic- z-pynuiny 1
-CH 2 OC(SMe)=N-
z =
5-CF 3 -2-pyridinyl
S — TV^f* - ? -nvri H t n\r\
-CH 2 OC(=S)NMe-
z =
4-CF 3 -phenyl
^ 3 r J
-CH 2 OC(=S)NMe-
z =
4-OCF 3 -phenyl
3-OCF-3 -nhenvl
-CH 2 OC(=S)NMe-
z =
3-Cl-phenyl
4-Cl-ohenvl
-CH 2 OC(=S)NMe-
z =
3,5-diCl-phenyl
3-Me-phenyl
-CH 2 OC(=S)NMe-
z =
4-Me-phenyl
3 5-diMe-T>henvI
-CH 2 OC(=S)NMe-
z =
2-naphthalenyl
6-Me-2-nvridinv1
-CH 2 OC(=S)NMe-
z =
4-Me-2-pyridinyl
■ j v-» uii Yit -t. pj 1 luui y 1
-CH 2 OC(=S)NMe-
z =
5-CF 3 -2-pyridinyl
5 - \4e-2-T> vt*i H 1 nvl
-SCH 2 -
z =
2-Me-phenyl
~~) S-Hi A/f p-rihpTivl
-SCH 2 -
z =
3-CF 3 -phenyl
4-CF 3 -phenyl
-SCH 2 -
z =
4-Me-phenyl
4-/-Bu-phenyl
-SCH 2 -
z =
3-Cl-phenyl
4-Cl-phenyl
-SCH 2 -
z =
2-Me-5-Cl-phenyl
3-f-Bu-phenyl
-SCH 2 -
z =
2-naphthalenyl
1-naphthalenyl
-SCH 2 -
z =
3-pyridinyl
4-pyridinyl
-SCH 2 -
z =
6-Me-2 -py ridinyl
5,6 ) 7,8-tetrahydro-2-
naphthalenyl
WO 99/28305
PCT/US98/24265
68
Y
Column 1
Column 9
-CH 2 0-N=C(SCH 3 )-
Z =
3-CF 3 -phenyl
3-OPF->-nhf»nv1
-CH 2 0-N=C(SCH 3 )-
Z =
3-Me-phenyl
*T-\^r 3 -pnenyi
-CH 2 0-N=C(SCH 3 )-
z =
4-OCF 3 -phenyl
4-Me-phenyl
-CH 2 0-N=C(SCHo)-
z =
3-Cl-nhenvl
j r j-aiv^i-pnenyi
-CH 2 0-N=C(cyclopropyl)-
z =
3-CFi-phenyl
3-OCFi-nhenvl
-CH 2 0-N=C(cyclopropyl)-
z =
3-Me-phenyl
4-CF 3 -phenyl
-CH 2 0-N=C(cyclopropyl)-
z =
4-OCF 3 -phenyl
4-Me-phenyl
-CH 2 ON=C(cyclopropyl)-
z =
3-Cl-phenyl
3,5-diCl-phenyl
Table 3b
= C1
Y
Column 1
Column 2
-O-
z =
Phenyl
3-OlMe-nHpnvl
-O-
z =
4-CF 3 -phenyl
3 -Me-nh envl
-O-
z =
3-F-phenyl
3-OCF-j -ohenvl
-O-
z =
4-Me-phenyl
3-I-phenyl
-O-
z =
3-SCH 3 -phenyl
2-Me-phenyl
-O-
z =
3-SCHF 2 -phenyl
4-SCHi -ohenvl
-O-
z =
3-cyclohexyl-phenyl
4-SCHF 2 -phenyl
-O-
z =
6-CF 3 -2-pyridinyl
5-CF 3 -2-pyridinyl
-O-
z =
4-CF 3 -2-pyridinyl
6-Me-2-pyridinyl
-O-
z =
6-(CF 3 CH 2 0)-4-pyrimidinyl
5-Me-2-pyridinyl
-O-
z =
2-(CF 3 CH 2 0)^-pyrimidinyl
4-(CF-3CH->0)-2-nvrimidinvl
-O-
z =
4-Me-2-pyridinyl
3,5-diMe-phenyl
-O-
z =
2-naphthalenyl
5,6,7,8-tetrahydro-2-
naphthalenyl
-O-
z =
4-OCF 3 -phenyl
3-f-Bu-phenyl
-O-
z =
4-f-Bu-phenyl
6-(CF 3 CH 2 0)-2-pyra2inyl
-O-
z =
3-SCF 3 -phenyl
4-SCF 3 -phenyl
-O-
z =
4-CF 3 -6-Me-2-pyridinyl
3-CN-phenyl
-O-
z =
4,6-diMe-2-pyridinyl
3,5-di(CF 3 )-phenyl
-O-
z =
5-Cl-2-thiazolyl
5-I-2-thiazolyl
-O-
z =
5-OCF 3 -2-thiazolyl
5-(CH 3 ) 3 Si-2-thiazolyl
-O-
z =
5-CN-2-thiazolyl
5-SCH 3 -2-thiazolyl
-O-
z =
5-CF 3 -2-thiazolyl
4-Me-5-Cl-2-thiazolyl
-O-
z =
4-Me-5-I-2-thiazolyl
4-Me-5-CN-2-thiazolyl
WO 99/28305
PCT/US98/24265
69
Y
Column 1
Column 2
-O-
Z =
4-Me-5-CF 3 -2-thiazolyl
-O-
Z =
3-(HCsC)-phenyl
3-(CH 3 C=C)-phenyl
-o-
Z =
3-((CH 3 ) 3 CC=C)-phenyl
3-((CH 3 ) 3 SiC=C)-phenyl
-o-
Z =
3-( [>— CSEEQ-phenyl
5-Me-2-thienyl
-o-
Z =
5-(CH3)3C-2-thienyl
-0-
Z =
5-Br-2-thienyl
5-I-2-thienvl
-o-
Z =
4-Me-2-thienyl
ijril. ") ttliotvwl
-o-
Z =
4-Cl-2-thienyl
t*Di-z- uiicnyi
-o-
Z =
4-I-2-thieny]
j -aiivie-z-tiiienyi
-o-
Z =
4-Me-5-Cl-2-thienyl
t-ivic-j-Dr-z-uiienyi
-o-
Z =
4-Me-5-I-2-thienyl
j-v^i-z-tiiienyi
-o-
Z =
5-Me-3-thienyl
3-^1-13,13 c-^-tnienyl
o
Z =
5-Cl-3-thienyl
j -or - o -uiieny i
-o-
Z =
5-I-3-thienyl
*t-ivic- j -iniciiyi
-o-
Z =
4-(CH 3 ) 3 C-3-thienyl
4- P 1 J\ -th i pn\/t
-o-
Z =
4-Br-3-thienyl
"T _ i"»7™ uuciiyi
-o-
Z =
4,5-diMe-3-thienyl
4-Mp-S-r'1-^-thir>r»\/1
*t"iYic j uiicnyi
-o-
Z =
4-Me-5-Br-3-thienyl
4 -M £» - S - T- - th t #*n u 1
■ IVIC ^"J.~J""tllICIiyi
-o-
Z =
2-Cl-3-thienyI
\—s± x uiivuyi
-CH 2 CJ-
Z =
Phenyl
x ~2 -pucny I
-CH 2 0-
Z =
2-Me-5-/-Pr-phenyl
^-ivic-H-v-'^xi^-pnenyi
-CH 2 0-
z =
4-OCF 3 -phenyl
*- j 3 pncuy i
-CH 2 0-
z =
3-OCHF 2 -phenyl
4-OPHF -» -nhenvl
-CH 2 0-
z =
3,5-di(CF 3 )-phenyl
x-ivic-t-v/^iiF o-pncnyi
-CH 2 0-
z =
6-CF 3 -2-pyridinyI
j v/v^ r 3 -pnenyi
-CH 2 0-
z =
4-CF-j-2-DVridinvl
" ivic - z-pynciinyi
-CH 2 0-
z =
2-Me-4-OCF 3 -phenyl
j -ivie-z.-py nainy i
-CH 2 0-
z -
3,6-diMe-2-pyridinyl
-CH 2 0-
z =
4,6-diMe-2-pyridinyl
o-v-^,r 3 -z-pynainyi
-CH 2 0-
z =
4-CF 3 -6-Me-2-pyridinyl
3-Me-2-pyridinyl
-CH 2 0-
z =
4-Cl-2-pyrimidinyl
6-Me-2-pyridinyl
-CH 2 0-
z =
4-Cl-2-pyrimidinyl
3-Et-phenyl
-CH 2 0-
z =
2,6-diMe-4-pyridinyl
2,4,6-triMe-phenyl
-CH 2 0-
z =
3-Cl-2-pyridinyl
6-Cl-4-pyrimidinyl
-CH 2 0-
z =
1-napthalenyl
2,3,6-triMe-phenyl
-CH 2 0-
z =
6-Cl-2-pyrazinyl
4-CF 3 -2-pyrimidinyl
WO 99/28305
PCTAJS98/24265
70
Y
Pftllimn 1
V_^U1 Ulliil 1
Column 2
-CH2O-
7 =
o~^r 3 pynniiuinyi
2-/-Pr-phenyl
-CH 2 0-
7 -
<»rt/lp. /.Ti\/nninnl
j ivxc".&~pyi lumy 1
4- ci-z -pynainy 1
-OCH2-
2 =
z.-ivic-pncijy 1
i c J;t/i„ _l _____ .1
2,5-aiMe-pnenyl
-OCH 2 -
Z =
5 -CF i -nhenvl
-phenyl
-OCH2-
2 =
^ *ivi c -p 1 icily 1
4-r-t>u-pnenyl
-OCH2-
7 —
j -^i-pneny 1
4-Cl-phenyI
-OCH2-
7 —
z-jvieo-^i-piienyl
3-/-Bu-phenyl
-OCH 2 -
7 =
£. -iiapninaienyi
1-naphthalenyl
-OCH 2 -
7 —
3-pyndinyl
4-pyridinyl
-OCH->-
7 —
6 -IVf e -2 -pyndiny 1
2-(5,6,7,8-
tetrahydro)naphthalenyl
-CHoO-N=C( - CHi
7 —
3-Me-phenyl
4-CF 3 -phenyl
-CH">0-N=C/CH->V
7 —
3,5- diMe -phenyl
3-Cl-phenyl
-CH-jO-N=CCCH^
7 —
4-Br-phenyl
3,5-di(CF 3 )-phenyl
-CH-)0-N=C/CH-> 1-
7 —
4-/-Bu-phenyl
-CH->0-N=CCCHo V
7 —
3-/-Bu-phenyl
5-CF 3 -2-pyridinyl
-CFfoO-N=C(CH^ V
7 —
A nlianirt
^-uL^r^-pnenyi
3-OCHF2-phenyl
-CH20-N=C(CH3>-
z =
j ivic-z -pynainy i
4-Cr 3 -6-Me-2-pyndinyl
-CH 2 0-N=C(CH 3 )-
2 =
*T-ivie -pynainy i
4,o-diMe-2-pyndinyl
-CH->0-N=C(CH?V
7 =
o-ivie-z -pynainy i
6-CF 3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )-
2 =
6-01\^e -2-nvri Hi ti vl
v» vi'iv *m i/yiiuuiyJ
2,6-diMe-4-pyndinyl
-CHoO-N=C(CH^V
2 =
^ , u**u.iv-'i-*t-py nuiny i
5-UOr 3 -2-pynainyl
-CH20-N=C(CH3>-
7 —
■f - ^jYie-z-pynuiny I
4-OCF3 -2-pyndmyl
-CH 2 0-N=C(CH3)-
2 =
j-u^nr 2 ^ "pyriaiiiyi
o-UCr 3 -2-pynainy 1
-CH 2 0-N=C(CH 3 )-
2 =
f-uLnr 2 pyncunyi
3-(CF 3 CH 2 0)phenyl
-CH 2 0-N=C(CH 3 )-
2 =
u~\-/^rxr 2 z -pynainy i
j-fct-pnenyi
-CH-?0-N=CCCH^V
7 =
1 -naphthaleny 1
1 ,2,3,4-tetrahydro-2-
naphthalenyl
-CH->0-N=CCCHi V
/ * —
3-SMe-phenyl
3-ethynylphenyl
-CH->0-N=C('CHi'>-
7 =
t T3n
rOU
2-F-5-CF 3 -pnenyl
-CH=N-OCH(CHi)-
z =
4-CF-a-Dhenvl
a— 1^ W*» .nnom/1
j v^/i uiiciiyi
-CH=N-OCH(CH 3 )-
z =
4-OCF 3 -phenyl
3-OCF 3 -phenyl
-CH=N-OCH(CH 3 )-
z =
3-Cl-phenyl
4-Cl-phenyl
-CH=N-OCH(CH 3 )-
z =
3,5-diCl-phenyl
3,5-di(CF 3 )-phenyl
-CH=N-OCH(CH 3 )-
z =
3-Me-phenyl
4-Me-phenyl
-CH=N-OCH(CH 3 )-
z =
2-naphthalenyl
4-OCHF 2 -phenyl
-CH=N-OCH(CH 3 )-
z =
3-OCHF 2 -phenyl
4-CF 3 -2-pyridinyl
WO 99/28305
PCT/US98/24265
71
Y
Column 2
-CH=N-OCH(CHiV
7 —
C r^T7 ^ ... ,,•11 1
o-^r 3 -z-pynainyl
6-CF3 -2-pyridiny 1
-CH=N-OCH(CH 3 )-
z =
4-Me-2-pyridinyl
5-Me-2-pyridinyl
-CH=N-OCH(CH3)-
Z —
6-Me-2-pyridinyl
4-CF3-6-Me-2-pyndinyI
-CH=N-OCH( CHi V
^mrM. M. A Will VilJ P
7 —
Z* —
4-(JCr3-z-pynainyl
5-OCF 3 -2-pyridinyl
-CH=N-OCH(CH 3 )-
7 —
6-OCF3 -2-pyndinyl
4-OCHF 2 -2-pyndinyl
-CH=N-OCHf CH-> 1-
7 —
Z —
^ -uuhr 2"^"py n " m y^
6-OCHF 2 -2-pyridinyl
-CH=N-OCHCCH-i V
3 -f -ou-pneny 1
4-/-Bu-phenyl
-CHo-SC(Ef>=N-
7 —
Z, —
4-Cr3-pnenyl
3-CF3-phenyl
-CHo-SC(Ef)=N-
7 —
z —
*t-vJL, r 3 -pnenyl
3-OCF 3 -phenyl
-CHo-SCfEf>=N-
7 —
Z, —
3-L-i-pnenyi
4-Cl-phenyl
-CH->-SC<Ef>=N-
7 —
j,s-aiCl-pnenyI
3,5-di(CF 3 )-phenyl
-CH">-SCfEf>=N-
7 —
Z. —
3-Me-phenyl
4-Me-phenyl
-CHo-SC(Ert=N-
7 —
Z, —
i,D -ai Me-paeny 1
2-naphthalenyl
7 —
z, —
6-Me-2-pynainyl
4-Me-2-pyridinyl
-CH->-SCfEf>=N-
7 —
Z —
4,6-diMe-2-pyridinyl
5-Cl-2-pyridinyl
7 —
z. —
4,6-aiCI-2-pyndinyl
5-Me-2-pyridinyl
-CH->-SC(Ett=N-
7 —
Zj
5-CF3-2-pyridinyl
5-Br-6-Me-2-pyridinyl
-CHo-SCf^SINMe-
7 —
Z- —
3 -pnenyl
3-CF3-phenyl
-CH->-SC(=S'>NMe-
7 —
z. —
4-UL.i , 3-pnenyJ
3-OCF 3 -phenyl
-CH->-SCC=S1NMe-
7 —
Zi —
j-v^i-pnenyi
4-Cl-phenyl
-CH->-SCf=SYNMe-
7 —
z —
j,j-aiLl-pnenyl
3,5-di(CF 3 )-phenyl
-CHo -SCr=S1NMe-
7 —
z. —
3-Me-phenyl
4-Me-phenyl
-CHo -SC(=S'iNMe-
z, —
3,5-diMe-phenyl
2-naphthalenyl
-CH 2 -SC(=S)NMe-
7 =
6-Me-2-pyridinyl
4-Me-2 -py ridinyl
-CH 2 -SC(=S)NMe-
2 =
4,6-diMe-2-pyndinyl
5-Cl-2-pyridinyl
-CH 2 -SC(=S)NMe-
Z =
HjO-uiv^i-z-pynumyi
5-Me-2-pyridinyl
-CH->-SC(=SYNMe-
7 =
z«
j-L-r 3 -z-pynainyi
5-Br-6-Me-2-pyndinyl
-CH 2 SC(SMe)=N-
Z =
3-Me-phenyl
4-Me-phenyl
-CH-> SCfSMe V=N-
7 —
Z. —
j,5-aLMe-phenyl
3-Cl-phenyl
-CH-> SCfSMet=M-
7 —
z. —
y| /"II ] *
4-Cl-pnenyI
3,5-diCl-phenyl
-CH 2 SC(SMe)=N-
z =
4-CF3*phenyl
-CH 2 SC(SMe)=N-
z =
3-OCF3 -phenyl
4-OCF 3 -phenyl
-CH 2 SC(SMe)=N-
Z =
3,5-di(CF 3 )-phenyl
CH 2 CH 2 -f-Bu
-CH 2 SC(SMe)=N-
Z =
t-Bu
2-naphthalenyl
-CH 2 SC(SMe)=N-
z =
6-Me-2-pyridinyl
4-Me-2-pyridinyl
-CH 2 SC(SMe)=N-
z =
4,6-diMe-2-pyridinyl
5-Cl-2-pyridinyl
-CH 2 SC(SMe)=N-
z =
4,6-diCl-2-pyridinyl
5-Me-2-pyridinyl
WO 99/28305
PCT/US98/24265
72
Column 1
roliimn 9
-CH 2 SC(SMe)=N-
2 =
5-CF-i -2-pyridinvl
-CH 2 S-
z =
2-Me-phenyl
j y^r 3 -pneny i
-CH 2 S-
Z =
4-CF^-Dhenvl
2,5-diMe-phenyl
-CH 2 S-
Z =
2-Et-phenyl
o-^i-pnenyi
-CH 2 S-
Z =
2-Cl-t>henvl
x,D-aiUi-pnenyl
-CH 2 S-
Z =
4.6-di\£e-2-r)vrirnidinvl
H-ivie- 1 ,z,*f-inazoi-3-yl
-CH 2 S-
z =
2-nanhthalf»Tiv1
1 X^a T ■ ■ ■ i * 1 1 ii 1 1
i -Me-2-imiaazolyl
-CH 2 S-
z =
*t—ivi c-x-py irrniuiny i
5-Me- 1 ,3,4-thiadiazol-2-yl
-CH 2 0-N=C(CH'j)CH9S-
Z =
~jiv.iv |j iici jy i
2-Me-phenyl
-CH 2 0-N=C(CH,)CH 9 S-
z =
4-CF 3 -phenyl
-CH 2 0-N=C(CH^)CH 9 S-
z =
^-Pl -nhenvl
2-Et-phenyl
-CH 2 0-N=C(CH?)CHoS-
z =
~ v—i piiciiyi
2-naphthalenyl
-CH 2 0-N=C(CH 3 )CH 2 S-
Z =
4-Cfr 3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
^...\/fo_r>V"its|-i\/l
i vie l/i J CUV 1
2-Me-phenyl
-CH 2 0-N=C(CH,)CH 9 O-
Z =
4 — IMf p*nhpnul
3-Cr3-phenyl
-CH 2 0-N=C(CH 3 )CH->0-
Z =
4-CF-» -nhenvl
**-d-pnenyj
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
3-Cl-phenyl
3,5-diMe-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
2 -5 - diMe -r)h en vl
z-ivieo-z-rT-pnenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
3-Et-phenyl
v-^f ^-z-pynainyi
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
4-CF 3 -2-pyridinyl
j-^Fj-z-pynamyi
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
6-Me-2-pyridinyl
J J.vic-x _ ^)yiiuiiiyi
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
4-Me-2-pyridinyl
i -napninaienyi
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
2-nanhthalenvl
z-cr 3 -pnenyi
-CH 2 CH 2 -
z =
2-Me-phenyl
2,5-diMe-phenyl
-CH 2 CH 2 -
z -
3-CF^-phenyl
^f-cr 3 -pnenyj
-CH 2 CH 2 -
z =
3-Cl-phenyl
4-i lannpnut
-CH 2 CH 2 -
z =
3-OCF3~phenyl
*t - wur 3 -pneny i
-CH 2 CH 2 -
Z =
2-Et-phenyl
x-ivie-j-^i-pncnyi
-CH 2 CH 2 -
z =
2-naohthalenvl
j,o-aiMe-z-pynainyl
-CH=C(CH,)-
z -
*X «* A/f P_T"\VlP>T"l\/l
j ivic— j/iicixy i
4-Me-phenyl
-CH=C(CH 3 )-
z =
3,5-diMe-phenyl
3-Cl-phenyl
-CH=C(CH 3 )-
z =
4-Cl-phenyl
3-OCF 3 -phenyl
-CH=C(CH 3 >
z =
4-OCF 3 -phenyl
3-CF 3 -phenyl
-CH=C(CH 3 )-
z =
4-CF 3 -phenyl
2-naphthalenyl
-CH=C(CH 3 )-
z =
4-CF 3 -2-pyridinyl
6-CF 3 -2-pyridinyl
-CH=N-N=C(CH 3 )-
z =
3-Me-phenyl
4-Me-phenyl
-CH=N-N=C(CH 3 )-
z =
3 -CF 3 -phenyl
4-CF 3 -phenyl
WO 99/28305
PCT/US98/24265
73
Y
Column 1
Column 2
-CH=N-N=C(CH 3 )-
Z =
3-OCF-j-phenyl
4-OCFi -nhenvl
■ 1 UUCLLY1
-CH=N-N=C{CH 3 )-
Z =
3,5-diMe-phenyl
-> v^i-pncnyi
-CH=N-N=C(CH 3 )-
7, =
4-Cl-phenyl
-CH=N-N=C(CH 3 )-
Z =
4-CF 3 -2-pyridinyl
»> v_/r3-z,-pynuinyi
-CH=N-N=C(CH 3 )-
Z =
6-CF 3 -2-pyridinyl
I\n _mf rin in\rl
~ ivic ~ z> yy 1 lumy i
-CH=N-N=C(CH 3 >
Z =
5-Me-2-pyridinyl
ft— nA p - v — H t tit t 1
v ivic-z.— jjyiiumy 1
-CH=N-N=C(CH 3 )-
Z =
2-naphthalenyl
*t,u-uij.vjLc-z.-pynumyi
-CH=N-N=C(CH 3 )-
Z =
3-Et-phenyl
# Tin
roll
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
3 -Me-phenyl
H-ivie-pnenyi
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
3 , 5-diM!e-pheny 1
j-^i-pnenyi
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
4-Gl-phenyl
j-uid-pnenyi
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
3-CF 3 -phenyl
^ v^r^-pncnyi
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
3,5-di(CF 3 )-phenyl
«j w^, 1 2 -pneny]
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
4-OCFo -phenyl
CH3
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
/-Bu
x-iiapniuaicnyi
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
4-/-Bu-phenyI
*T-iYic-i-pyiiuiJiyi
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
5-Me-2-pyridinyl
r\ — "\At> _ 0 _t"i\/i"i H i Tt 1 t 1
u-ivic-x -£iy 1 luiiiy i
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
4-CF 3 -2-pyridinyl
5-CF^ -2-ovridinvl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
6-CF-j -2-pyridinyl
4 6-diMe-2-nvridinvl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-CF 3 -2-pyrimidinyl
j <s> ^1 y i uxiiuiiiy I
-CH=N-N(CH 3 )-
Z =
3-Me-phenyl
4-Me-nh en vl
-CH=N-N(CH 3 )-
z =
3,5-diMe-phenyl
3-Cl-phenyl
-CH=N-N(CH 3 )-
z =
4-Cl-phenyl
3,5-diCl-phenyl
-CH=N-N(CH 3 )-
z =
3-CFo -phenyl
4-CFt -nhenvl
-CH=N-N(CH 3 )-
z =
3-OCF 3 -phenyl
4-OCF-j -nhenvl
-CH=N-N(CH 3 >
z =
2-naphthalenyl
4-f-Bu-nhenvl
-CH=N-N(CH 3 >
z =
4-Me-2-pyridinyl
S — lvfp — 0 — nvri H i nvl
— ' IVit x. p V 1 ILUIIY X
-CH=N-N(CH 3 )-
z =
6-Me-2-pyridinyl
t-v_^x T *• jjyiiuuiyi
-CH=N-N(CH 3 >
z =
5 -CF3 -2-pyridinyl
vj Vw. i 3 iuiii y 1
-CH=N-N(CH 3 >
z =
4,6-diMe-2-pyridinyI
*r-v^ f 3 ^ pyi liniumyi
-CH 2 OC(SMe)=N-
z =
4-CF3-phenyl
3-CF^ -phenyl
-CH 2 OC(SMe)=N-
z =
4-OCF 3 -phenyl
3-OCF 3 -phenyl
-CH 2 OC(SMe)=N-
z =
3-Cl-phenyl
4-Cl-phenyl
-CH 2 OC(SMe)=N-
z =
3,5-diCl-phenyl
3-Me-phenyl
-CH 2 OC(SMe)=N-
z =
4-Me-phenyl
3,5-diMe-phenyl
-CH 2 OC(SMe)=N-
z =
2-naphthalenyl
6-Me-2-pyridinyl
-CH 2 OC(SMe)=N-
z =
4-Me-2-pyrid i nyl
4,6-diMe-2-pyridinyl
WO 99/28305
PCT/US98/24265
74
Y
Column 1
{""nllimn 7
V • VJ 1 H 1 1 1 1 1 ^
-CH 2 OC(SMe)=N-
z =
5-CF 3 -2-pyridinyl
•J avj.g-^.— pyii\uny i
-CH 2 OC(=S)NMe-
z =
4-CF 3 -phenyl
j— \^r 3 -^jiiciiyi
-CH 2 OC(=S)NMe-
z =
4-OCFvphenyl
3-OCF-j -nhenvl
-CH 2 OC(=S)NMe-
z =
3-Cl-phenyl
4-C 1 -n hpn v 1
-CH 2 OC(=S)NMe-
z =
3,5-diCl-phenyl
3-Me-nhenvl
-CH 2 OC(=S)NMe-
z =
4-Me-phenyl
-CH 2 OC(=S)NMe-
z =
2-naphthalenyl
ft — \^ A 0 — tl\/T*i H i n 1/ 1
u ivic-i-pytiuujyi
-CH 2 OC(=S)NMe-
z =
4-Me-2-pyridinyl
^ ! D"Uuvic~^-pyiiuinyi
-CH 2 OC(=S)NMe-
z =
5-CF 3 -2-pyridinyl
j ivic-i-pyiiuuiyj
-SCH 2 -
z =
2-Me-phenyl
J UilVlC-£JIlCliy 1
-SCH 2 -
z =
3-CFvphenyl
4-CF^ -phenyl
-SCH 2 -
z =
4-Me-phenyl
•t- 1 -D U-L/lIcJiy 1
-SCH 2 -
z =
3-Cl-ohenvl
/I r* 1 _T\Knm /I
**- v_-i-pncny i
-SCH 2 -
z =
2-Me-5-Cl-phenyl
j-i-D u-pncnyi
-SCH ? -
z =
2-naohthalenvl
i -napninaieny l
-SCH->-
z =
3-nvriHinvl
4-pyndinyl
-SCH 2 -
z =
6-^^e-2-nvriHin\/1
v uiv ^* ujiiuuiyi
j,o, /,o-ieiranyaro-i-
uapniaaiejiyi
-CH 2 0-N=C(SCH 3 )-
z =
3 -CF^ -phenyl
^~v_xv^f o -pneiiyi
-CH 2 0-N=C(SCH 3 )-
z =
3-Nf e-nhenvl
f-^r^-pnenyi
-CH 2 0-N=C(SCH 3 )-
z =
4-OCF 3 -phenyl
4-Me-phenyl
-CH 2 0-N=C(SCH 3 >
z =
3-Cl-nhenvl
j,j-Qi^i-pnenyi
-CH 2 0-N=C(cyclopropyl)-
z =
3-CFo-Dhenvl
-CH 2 0-N=C(cyclopropyl)-
z =
3-Me-phenyl
4-C Fo -nh vl
-CH 2 0-N=C(cyclopropyl)-
z =
4-OCF 3 -phenyl
4-Me-phenyl
-CH 2 0-N=C(cyclopropyl)-
z =
3-Cl-phenyl
3,5-diCl-phenyl
Table 3 c
= CF 3
Y
Column 1
Column 2
-O-
z =
Phenyl
3-OMe-phenyl
-O-
z =
4-CF 3 -phenyl
3-Me-phenyl
-O-
z =
3-F-phenyl
3-OCF 3 -phenyl
-o-
z =
4-Me-phenyl
3-I-phenyl
-o-
z =
3-SCH 3 -phenyl
2-Me-phenyl
-o-
z =
3-SCHF 2 -phenyl
4-SCH 3 -phenyl
WO 99/28305
PCT/US98/2426S
75
Y
■ Column 1
coiuinn z
-O-
7 =
3-cyclohexyl-phenyl
4-SCHF 2 -phenyl
-O-
z =
6-CF3 -2-pyridinyl
j ~*—r^ * pynmnyi
-o-
z =
4-CF*a -2-ovridinvl
6-Me-2-pyridinyI
-o-
z =
6-fCFiCHoOV4-Dvrimidinvl
1— nAf*— *? — ty\/t"i rl iti\/1
J ~ Ir 1C ~ ^ ~p 1 1 uuiy I
-o-
z =
2-(CFiCH')0 , )-4-Dvrimidinvl
**-^r 3*w.ri2 l - , y~^~pynmiainyi
-o-
z =
4-Ntf e-2 -nvri di nvl
3,5- diMe-pheny 1
-o-
z =
2-naphthalenyl
j,o, / ,o-ic li anyaro- z-
nap ninaieny 1
-o-
z =
4-OCF3-phenyl
o 1 ±j u pncnyi
-o-
z =
4-f-B u-pheny I
o-^r $\^ti2V)-z -pyrazinyl
-0-
z =
3 -phenyl
-o-
z =
~ 3 v^J-vic -z -pynuinyi
J-CN-pnenyl
-o-
z =
~> w . uiiv-ic-^-pyriaiiiyi
3,5-di(CF 3 )-phenyl
-o-
z =
5-Cl-2-thiazolvl
o - i-x-niiazoiy J
-o-
z =
5-(CH 3 ) 3 Si-2-thiazolyl
-o-
z =
5-CN-2-thiazolyl
-O-
z =
5-CF 3 -2-thiazolyl
4-Me-5-CI-2-thiazolyl
-o-
z =
4-Me-5-I-2-thiazolyl
4-Me-5-CN-2-thiazolyl
-o-
z =
4-Me-5-CF 3 -2-thiazolyl
-o-
z =
3-(HC=C)-phenyl
3-(CH 3 C=C)-phenyl
-o-
z =
3-((CH 3 ) 3 CC=C)-phenyl
3-((CH 3 ) 3 SiC=C)-phenyl
-O-
z =
3-( [>-C=C)-phenyl
5-Me-2-thienyl
-o-
z =
5-(CHoHC-2-thienvl
9 ttiio-ni/I
j-^i-z-uuenyi
-o-
z =
5-Br-2-thienyl
5-I-2-thif»nvl
-o-
z =
4-Me-2-thienyl
*T-^ri3J3^ -z -unenyi
-0-
z =
4-Cl-2-thienyl
*t ~xsr-^- uiicny 1
-o-
z =
4-1-2 -thienyl
n,D-uiJYLc-z-uiienyi
-o-
z =
4-Me-5-Cl-2-thienv1
^-ivie-j-r>r-z-tnienyl
-o-
z =
4-Me-5-T-2-thienv1
j -ci -z - tmenyi
-o-
z =
5-Me-3-thienyl
-o-
z =
5-Cl-3-thienyl
5-Br-3-thienyl
-o-
z =
5-I-3-thienyl
4-Me-3 -thienyl
-o-
z =
4-(CH 3 ) 3 C-3-thienyl
4-Cl-3-thienyl
-o-
z =
4-Br-3-thienyl
4-I-3-thienyl
-o-
z =
4,5-diMe-3-thienyl
4-Me-5-Cl-3-thienyl
-0-
z =
4-Me-5-Br-3-thienyl
4-Me-5-I-3-thienyl
WO 99/28305
PCT/US98/24265
76
Y
Column 1
v^oiunin z
-0-
Z =
2-Cl-3-thienyl
2-CF^ -phenyl
-CH 2 0-
z =
Phenyl
j-v-r a-pnenyi
-CH 2 0-
z =
2-Me- 5 -i-Pr-nhfm vl
z-ivie-^-(JCri3 -pnenyi
-CH 2 0-
z =
4-OCF 3 -phenyl
z-meo-cr^-pnenyi
-CH 2 0-
z =
3-OCHFo-nhenvl
• — u Crir 2 -pnenyi
-CH 2 0-
z =
3 5-difPF-»V.ntw*nv1
2-Me-4-OCHF 2 -phenyl
-CH 2 0-
z =
ft— f h 1 "** — V— nvWrlin'^/I
w V>1 "5 1"V ILllIiyi
3-OCF 3 -phenyl
-CH 2 0-
z =
4-Me-2-pyridinyl
-CH 2 0-
z =
4- \y\\^-<-t-\j\_,r 3 -pnenyi
5-Me-2-pyridinyl
-CH 2 0-
z =
3 6-dilVfe-P-nvrtHin\/l
uAiTit ^> [-> y 1 iuiny 1
D-Cr 3 -2-pynainyi
-CH 2 0-
z =
~»v unvAt-z-pyriuinyi
o-OCF 3 -2-pyndinyl
-CH 2 0-
z =
4-PF'5-fi-\/f P-9-rwriHin\/1
3-Me-2-pyridinyl
-CH 2 0-
z =
t-^i-z -pyriniiaiiiy 1
6-Me-2-pyridinyl
-CH 2 0-
z
z =
^-^A-z-pynmiainyi
3-Et-phenyl
-CH 2 0-
z =
J ft— fll IV 4p ^ rt*i fltrn rl
u- uuvic-*t -pynainy 1
2,4,6-tnMe-phenyl
-CH 2 0-
z =
3 — 4 1 - 7 — nvri rl i n u 1
pynuiuyi
o-Cl-4-pyrimidinyl
-CH 2 0-
z =
1 -fianti"isi1#MY\/1
* uauuiuiwiiyi
z^jO-trAMe-phenyl
-CH 2 0-
z =
ft -C* J - 7 — ti vra ti »ix / 1
\j v^i -*-~ijyi<i£iiiyi
4-CF 3 -2-pyrimidinyl
-CH 2 0-
z =
6-CFi-4-n.vrimidinvl
2-/-Pr-phenyl
-CH 2 0-
z =
— * a»*v *f pyiiuuiyi
H-ci-/-pynainyl
-OCH 2 -
z =
2-\f e-nh e n vl
^,5-aiMe-pnenyl
-OCH 2 -
z =
3-CF3-phenyl
4-CF 3 -phenyl
-OCH 2 -
z =
4-l^e-Dhenvl
^f-i-rtu-pnenyi
-OCH 2 -
z =
3-Cl-nhenvl
4-Cl-pnenyl
-OCH->-
z =
z. ivic-j-v^i-pncnyi
3-/-Bu-phenyl
-OCH 2 -
z =
2-naohth al en v 1
1 -naphthalenyl
-OCH 2 -
z -
3 -nvri H i n\/l
*-* yyiiKiiXiyi
4-pyridinyl
-OCH 2 -
z =
O -Mp-9-tivri H inv/l
v» ivaw <w pyiiumyi
O /C CIO
2-(5,6,7,8-
tetrahydro)naphthalenyl
-CH 2 0-N=C(CHo)-
z =
<j lvic uiicnyi
4-CF 3 -phenyl
-CH 2 0-N=C(CH 3 )-
Z
3 S— H iA/Tf*— r*h*an^/1
3-cl-pnenyl
-CH 2 0-N=C(CH 3 )-
z =
4-Br-phenyl
3,5-di(CF 3 )-phenyl
-CH 2 0-N=C(CH 3 )-
z =
4-OCHF 2 -phenyl
4-/-Bu-phenyl
-CH 2 0-N=C(CH 3 )-
z =
3-MJu-phenyl
5-CF 3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )-
z =
4-OCF 3 -phenyl
3-OCHF 2 -phenyl
-CH 2 0-N=C(CH 3 )-
z =
5-Me-2-pyridinyl
4-CF 3 -6-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )-
z =
4-Me-2-pyridinyl
4,6-diMe-2-pyridinyl
WO 99/28305
PCT/US98/24265
77
Y
Column 1
Column 9
^>VJ1 Ll.il 1 1 1 ^—
-CH 2 0-N=C(CH 3 )-
Z =
6-Me-2-pyridinyl
6-CF3 -2-pyndinyl
-CH 2 0-N=C(CH 3 )-
Z =
6-OMe-2-pyridinyl
2,6-diMe-4-pyridinyl
-CH 2 0-N=C(CH 3 )-
Z =
2, 6-diCl-4-pyridinyl
-CH 2 0-N=C(CH 3 )-
Z =
4-OMe-2-pyridinyl
**- i^i^r 3 --t-pyn amy 1
-CH 2 0-N=C(CH 3 )-
Z =
5-OCHF 2 -2-pyridinyl
u-v-i^F^-z-pynuinyj
-CH 2 0-N=C(CH 3 )-
Z =
4-OCHF 2 -pyridinyl
o-^^i^i^i^wjpneny]
-CH 2 0-N=C(CH 3 )-
Z =
6-OCHF*i-2-Tlvrifiin\/l
j-iit-pnenyi
-CH 2 0-N=C(CH 3 )-
z =
1 -nanhthalpnvl
1 5 2,3,4-tetranyaro-2-
naphthal eny I
-CH 2 0-N=C(CH 3 )-
z =
1 _i.i 11 1
3-ethynylphenyl
-CH 2 0-N=C(CH 3 )-
z =
f-Bu
2-F-5-CF 3 -phenyl
-CH=N-OCH(CH 3 )-
z =
4-CF 3 -phenyl
0 r 3 -pneny J
-CH=N-OCH(CH 3 )-
z =
4-OCF?-Dhenvl
^-DUr^-pnenyl
-CH=N-OCH(CH 3 )-
z =
3-Cl-t)henvl
4-CJ-pnenyl
-CH=N-OCH(CH 3 )-
z =
3,5-diCl-phenyl
j , o -ai^ 3 ^j-pnenyi
-CH=N-OCH(CH 3 )-
z =
3-Me-phenyl
4-Me-phenyl
-CH=N-OCH(CH 3 )-
z =
2-naphthalenyl
*t-w\^nr2 _ pnenyi
-CH=N-OCH(CH 3 )-
z =
3-OCHF 2 -phenyl
*f-v^r 3 -z-pynainyi
-CH=N-OCH(CHo)-
z =
5-CFo -2-nvridinvl
o-Ch 3 -i!-pynduiyl
-CH=N-OCH(CH 3 )-
z =
4-Me-2-pyridinyl
j "ivio-z-pyiiaijiy 1
-CH=N-OCH(CH 3 )-
z =
6-Me-2-pyridinyl
*t-v-r 3~o-ivie-z-pynQinyi
-CH=N-OCH(CH 3 )-
z =
4-OCFi-2-ovridinv1
-^-vj^r^-z-pynainyi
-CH=N-OCH(CH 3 )-
z =
6 - OCF3 -2-pyridiny 1
A-OfT-TP.-* 7 nvrtHimrl
h -v^v^rxr 2 ^-pynainyi
-CH=N-OCH(CH 3 )-
z =
5-OCHFo-2-nvridiriv1
o-vjL,xir 2"-6"pyTiciinyi
-CH=N-OCH(CH 3 )-
z =
3-/-Bu-phenyl
4-tf-Bu-phenyl
-CH 2 -SC(Et)=N-
z =
4-CF 3 -phenyl
j"V^r 3 -pneiiyi
-CH 2 -SC(Et)=N-
z =
4-OCF 3 -phenyl
j-vjL-r 3 -pnenyi
-CH 2 -SC(Et)=N-
z =
3-Cl-phenyl
**~v^i-pncnyi
-CH 2 -SC(Et)=N-
z =
3,5-diCl-phenyl
j, j~uiv i v^F3^-pnenyi
-CH 2 -SC(Et)=N-
z =
3-Me-phenyl
t-ivic-pnenyi
-CH 2 -SC(Et)=N-
z =
3,5-diMe-phenyl
2-naphthalenyl
-CH 2 -SC(Et)=N-
z =
6-Me-2-pyridinyl
4-Me-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
4,6-diMe-2-pyridinyl
5-Cl-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
4,6-diCl-2-pyridhiyl
5-Me-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
5-CF 3 -2-pyridinyl
5-Br-6-Me-2-pyridinyl
-CH 2 -SC(=S)NMe-
z =
4-CF 3 -phenyl
3-CF 3 -phenyl
-CH 2 -SC(=S)NMe-
z =
4-OCF 3 -phenyl
3-OCF 3 -phenyl
WO 99/28305
PCT/US98/24265
78
Y
Column 1
f'rtlllTTlTl 0
x— -Ul UII LI 1 £.
-CH 2 -SC(=S)NMe-
Z =
3-Cl-phenyl
*t~ k> i-pncny i
-CH 2 -SC(=S)NMe-
z =
3,5-diCl-phenyl
j^j-ui^r^ _j-pneny i
-CH 2 -SC(=S)NMe-
z =
3-Me-phenyl •
4-Me-phenyl
-CH 2 -SC(=S)NMe-
z =
3,5-diMe-phenyl
z-nap ninaieny i
-CH 2 -SC(=S)NMe-
z =
6-Me-2-nvridinvl
V 1T4V ^ rJ * J
4-Me -2 -pyridiny 1
-CH 2 -SC(=S)NMe-
z =
4 , 6- diMe-2-py ri diny I
j-v-i-z-pynainy]
-CH 2 -SC(=S)NMe-
z =
4 6-diCI-2-nvridinv1
5-Me-2-pyridinyl
-CH 2 -SC(=S)NMe-
z =
5-CF-5 -2-nvridinvl
o-or-o-Me-z-pyndinyl
-CH 2 SC(SMe)=N-
z-
3 -Me-pheny 1
4-Me-phenyl
-CH 2 SC(SMe)=N-
z =
3 5-diMe-r>henvl
J-t-i-pnenyl
-CH 2 SC(SMe)=N-
z =
4-Cl-Dhenvl
j.j-aiu-pnenyl
-CH 2 SC(SMe)=N-
z =
3-CFi -nhenvl
^-Lr 3 -pnenyi
-CH 2 SC(SMe)=N-
z =
3-OCF 3 -phenyl
^ uur 3 ~pncnyi
-CH 2 SC(SMe)=N-
z =
3,5-di(CF-i)-phenyl
CHiC"H->-/-Rii
-CH 2 SC(SMe)=N-
z =
r-Bu
«£■ iiapuuialCIiyi
-CH 2 SC(SMe)=N-
z =
6-Me-2-pyridinyl
t-ivie-z^ -pynuuiyi
-CH 2 SC(SMe)=N-
z =
4,6-diMe-2-pyridinyl
S-fl - 9 -n vri H t n vl
-CH 2 SC(SMe)=N-
z =
4,6-diCl-2-pyridinyl
i— ft^P - V — Y\ vri H i twl
-CH 2 SC(SMe)=N-
z =
5-CF-i-2-pyridinyl
S-ftr-fj-\4p-9-r»VT"irlin\/1
-CH 2 S-
z =
2-Me-phenyl
3-CF3 -pheny 1
-CH 2 S-
z =
4-CF-3 -nhenvl
2,5-diMe-phenyl
-CH 2 S-
z =
2-Et-phenyl
j -^--1-piieny 1
-CH 2 S-
z =
2-Cl-Dhenvl
^,j-uici-pnenyi
-CH 2 S-
z =
4,6-diMe-2-pyrimidinyl
*t-ivic- 1 ,z,*t-inazoi- j-yi
-CH 2 S-
z =
2-naphthalenyl
1 _ lV^^ ^ i nil ^ * 1
i -ivie-i-imiuoZuiyi
-CH 2 S-
z =
4-Me-2-Dvrimidinvl
j-ivie- 1 , j» fi r-iniau.iazol-z-yl
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
3-Me-phenyl
2-Me-phenyl
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
3-CF 3 -phenyl
4-CF3 -phenyl
-CH 2 0-N=C(CH 3 )CH 2 S-
z-
3-Ci-phenyl
2 -E t-pheny 1
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
4-Cl-Dhenvl
2 -naphthal eny 1
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
2,5-diMe-phenyl
4-CF-a -2-pyridiny 1
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
3-Me-phenyl
2-Me-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4-Me-phenyl
3-CF 3 -phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4-CF 3 -phenyl
4-Cl-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
3-Cl-phenyl
3,5-diMe-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
2,5-diMe-phenyl
2-Me-5-/'-Pr-phenyl
-CH 2 0-N=C(CH 3 )CH 2 O-
z =
3-Et-phenyl
6-CF 3 -2-pyridiny 1
WO 99/28305
PCT/US98/24265
79
Y
• Coluinn 1
^oiunin z
-CH 2 0-N=C(CH 3 )CH 2 0-
7 =
■ '* j -x.-yy 1 iuuiv x
3 -^r 3 -z-pynainy I
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
6-N4e-2-T)vridinvI
5-Me-2-pyndinyl
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
4- IVfe -2-iwri Hinvl
* «av yy 1 JUllly 1
1 -naphthaleny 1
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
z-cr^-pnenyl
-CHoCH-j-
z z
2 =
^.-iviv-pncnyi
2,5-aiMe-phenyI
-CHoCHo-
Z Z
2 =
-5 ^ pncny 1
4-CF 3 -phenyl
-CH 2 CH 2 -
^ Z
Z =
'fr-L-i-pnenyi
-CH 2 CH 2 -
z z
z =
3-OPF^-nhpnvl
4-UL.r 3 -pnenyl
-CH 2 CH 2 -
z. z
z =
5— Ft— nhf*nvl
ij l piicny 1
z-Me-D-ci-pnenyl
-CH 2 CH->-
z z
z =
J,o-aiMe-2-pyndinyl
-CH=C(CH 3 )-
2 =
j -ivic-piicny 1
4-Me-phenyl
-CH=C(CHa)-
2 =
-' s -j~uuvie-pncnyi
3-Cl-phenyJ
-CH=C(CH?)-
2 =
■ v^i pxiciiy j
3-OCF 3 -phenyl
-CH=C(CH 3 )-
2 =
^r-yjy^r 3 -pnenyi
3 -CF 3 -phenyl
-CH=C(CH 3 )-
2 =
t-^-r ^ pncny 1
2-napnthalenyI
-CH=C(CH 3 )-
2 =
*r v^r^ ^ pyriuinyj
o-Or 3 -2-pyndiny 1
-CH=N-N=C(CHo)-
2 =
j -ivi e-pneny i
4-Me-phenyl
-CH=N-N=C(CH,)-
2 ■
^ - F . rt \\ n \/l
v_/±r T -p ucuy 1
4-Cr 3 -phenyl
2 =
j - 3 -pnenyi
4-OCF 3 -phenyl
-CH=N-N=C(CH 3 )-
2 =
3 , 5 -diMe-pheny 1
3-Cl-phenyl
-CH=N-N=C(CH 3 )-
2 =
A^(~^\ _r\Vit»r^Tr1
*t~\-'i~piicnyi
3,5-diCI-phenyl
-CH=N-N=C(CH-i)-
2 =
*r-\^r 2 "Z-pynouiyi
5-CF3-2-pyndmyl
-CH=N-N=C(CH 3 )-
2 =
u~v-r 2 -z-pynuinyi
4-Me-2-pyridinyl
-CH=N-N=C(CH 3 )-
z =
S-A/f f*-9 »nvriH i n \/l
— ' i'lv x> li y i luiii y i
6-Me-2-pyridinyl
-CH=N-N=C(CH 3 )-
Z =
2-nanhthalfMivl
4,0-uiJYie-z-pynainyl
-CH=N-N=C(CH^)-
2 =
^ — P t"— n Vl AT1\/ 1
•j t piiviiy i
t-Gu
-CH 2 0-N=C(CH 3 )C(=NOCH,)-
2 -
3 -Tvf e-fihpnvl
4-Me-phenyl
-CH 2 0-N=C(CHo)C(=NOCH^)-
2 -
j , j-uiivic-pncnyi
j-Cl-pnenyl
-CH 2 0-N=C(CH-i)C(=NOCH-i)-
2 =
" v-^i~piicnyi
3,5-diCI-phenyl
-CH 2 0-N=C(CHa)C(=NOCHiV
2 =
j vr j -p ncny i
4-CF 3 -phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
3,5-di(CF 3 )-phenyl
3-OCF^-nhenvl
-CH 2 O-N=C(CH 3 )C(=N0CH 3 )-
Z =
4-OCF 3 -phenyl
CH 3
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
t-Bu
2-naphthalenyl
-CH 2 O-N=C(CH 3 )C(=N0CH 3 )-
Z =
4-/-Bu-phenyl
4-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
5-Me-2-pyridinyl
6-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
4-CF 3 -2-pyridiny 1
5-CF 3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
6-CF 3 -2-pyridinyl
4, 6-diMe-2-pyridiny 1
WO 99/28305
PCT/US98/24265
80
Y
Column 1
Pnlumn "7
CH 2 0-N=C(CH 3 )C(=NOCH*)-
Z =
4-CP"5 -2-nvrim irfinvl
6-CF3-2-pyriinidinyl
-CH=N-N(CH 3 )-
z =
3 -Me-pheny 1
*t"ivic-pnciiyi
-CH=N-N(CH 3 )-
Z =
3,5-diMe-phenyl
^-Pl-nhpm/l
-CH=N-N(CH 3 )-
Z =
4-Cl-phenyl
jjj* x-piiciiy 1
-CH=N-N(CH 3 )-
Z =
3-CF 3 -phenyl
-CH=N-N(CH 3 )-
z =
3-OCFi -Dhenvl
h— ^v^r^-pnenyi
-CH=N-N(CH 3 )-
Z =
2-naDhthalenvl
h-z-jd u-pneny 1
-CH=N-N(CH 3 )-
z =
4-A/f P— "7 _t-\\/t-i H * m/l
5-Me-2-pyridinyl
-CH=N-N(CH 3 )-
z =
1 vac ~ py i luiii y l
4-L.i- 3-2-pyndmyl
-CH=N-N(CH 3 )-
Z -
j- v^r" ^ -^"pyrioiny i
o-CF 3 -2-pynduiyl
-CH=N-N(CH 3 )-
z =
*t , u- uiivic- j& py nuinyi
4-Cb 3 -2-pynmidinyl
-CH 2 OC(SMe)=N-
z =
4— i F*^ — r^hpiivl
-r-v_..r 3-pucuyi
3-Cr 3 -pnenyl
-CH 2 OC(SMe)=N-
z =
4-OCF'> -Tihpnvl
->-UCr 3 -pnenyl
-CH 2 OC(SMe)=N-
z =
3-Cl-nhenvl
4-Cl-phenyl
-CH 2 OC(SMe)=N-
z =
3 5-diCl-nhenvl
3-Me-phenyl
-CH 2 OC(SMe)=N-
z =
4-A/f p— n ri pn \/1
i ivic piicxiyi
3,5-diMe-phenyl
-CH 2 OC(SMe)=N-
z =
0—n nnhtfasilpmsl
liopiiuwuciiyi
6-Me-2-pyridinyl
-CH 2 OC(SMe)=N-
z =
4 - — ^ — ti vri H i fi v 1
« j-vic yjy i iuiiiy i
4,6-diMe-2-pyridinyl
-CH 2 OC(SMe)=N-
z =
-2-nvridinv1
«■» 4 ^ pjf L lUuly i
5 -Me-2-pyridiny 1
-CH 2 OC(=S)NMe-
z =
4-CF^-nhenvl
j -i^r ^ pnenyi
-CH 2 OC(=S)NMe-
z =
4-OCF 3 -phenyl
j • 3 "jjiiciiy 1
-CH 2 OC(=S)NMe-
z =
3-Cl-phenyl
4—^1 — nVi An\/1
-CH 2 OC(=S)NMe-
z =
3,5-diCl-phenyl
-CH 2 OC(=S)NMe-
z =
4-Me-phenyl
j j j-uiivic "piiciiy 1
-CH 2 OC(=S)NMe-
z =
2-naphthalenyl
v ivic *i uyiiumyi
-CH 2 OC(=S)NMe-
z =
4-Me-2-pyridinyl
T5U-uii.vj.c- 4. py 1 luiiiyi
-CH 2 OC(=S)NMe-
z =
5 -CF 3 -2-pyridinyl
S — — "} — twn H i n \/1
<j i.vxc py 1 luuiy i
-SCH 2 -
z =
2-Me-phenyl
"7 S-HiA^p— T^hpfivl
"Uiivic - piiciiy i
-SCH 2 -
z =
3-CF 3 -phenyl
4-CF 3 -phenyl
-SCH 2 -
-4,
z =
4-N/Ie-'nhenvl
T-f-xJu-pnenyi
-SCH 2 -
z =
3-Cl-phenyl
4-C!l -n h en vl
-SCH 2 -
z =
2-Me-5-Cl-phenyl
3-J-Bu-phenyl
-SCH 2 -
z =
2-naphthalenyl
1-naphthalenyl
-SCH 2 -
z =
3-pyridinyl
4-pyridinyl
-SCH 2 -
z =
6-Me-2-pyridinyl
5,6,7,8-tetrahydro-2-
naphthalenyl
-CH 2 0-N=C(SCH 3 )-
z =
3 -CF3 -phenyl
3-OCF 3 -phenyl
WO 99/28305
PCT/US98/24265
81
Y
/"^rtlumti 1
V-.UIUII1I1 1
Column 2
-CH 2 0-N=C(SCH?)-
Z —
j -ivie-pnenyi
4-CF 3 -phenyl
-CH 2 0-N=C(SCH 3 )-
z =
4-OCF 3 -phenyl
4-Me-phenyl
-CH'>0-N=CfSCHaV
7 =
j-v^i-pnenyi
3,5-diCl-phenyl
-CH 2 0-N=C(cyclopropyl)-
» •* 1 XT J J
z =
^— l P** -Tlhf*Tlvl
3-UCr 3-pnenyl
-CH 2 0-N=C(cyclopropyl)-
z =
^ -MV*-nh pnvl
4-Cr 3-pnenyl
-CH 2 0-N=C(cyclopropyl)-
z =
4-OCFvpheny]
4-Me-ohenvl
-CH 2 0-N=C(cyclopropyl)-
z =
3-Cl-phenyl
3 5-diCI-nhpnvl
Table 4a
= CH 3
Y
Column 1
Column 2
-O-
z =
Phenyl
j-uivie-pnenyl
-O-
z =
4-CF->-nhenvl
3-Me-phenyl
-O-
z =
3 - P-r> h pnvl
J-ucr 3 -pnenyl
-O-
z =
j-i-pnenyl
-O-
z =
3-SCH-j-Dhenvl
z-rvie-pnenyi
-O-
z =
3-SCHF*>-nhpnvl
^-oCri3 -pneny 1
-O-
z =
3-cyclohexyl-phenyl
-O-
z =
6-CF 3 -2-pyridiny 1
j ^r3-z-pynainyi
-O-
z =
4-CF'a-2-t>vridinvl
6-Me-2-pyndinyl
-O-
z =
6-f CF^CHoOW-BViimidinv]
j -ivic-^-pyriQinyi
-O-
z =
2-(CFiCHoO)-4-Dvrimidinvl
H-^r3V^ri2^j-^-pynmiainyl
-O-
z =
4-Me-2-Dvridi nvl
j>,j -uiivic-pneiiy i
-O-
z =
2-naphthalenyl
S 7 R-t<="tmh\/Hrrv 9
JiU, / ,o-icixanyaro-^-
iiapiiuiai eny 1
-O-
z =
4-OCF3 -phenyl
*7 t u U"pxicuy i
-O-
z =
4-f-Bu-phenyl
-O-
z =
3-SCF 3 -phenyl
h- o r 3 -pnenyi
-O-
z =
5 -cjn -pnenyi
-o-
z =
4,6-diMe-2-pyridinyl
1 S-HifCP^-nhAfw/l
j yj ui\ \*-r 3 y pneny i
-o-
z =
5-Cl-2-thiazolyl
5-1-2-thiazolyl
-o-
z =
5-OCF 3 -2-thiazolyl
5-(CH 3 ) 3 Si-2-thiazolyl
-o-
z =
5-CN-2-thiazolyl
5-SCH 3 -2-thiazolyl
-o-
z =
5-CF 3 -2-thiazolyl
4-Me-5-Cl-2-thiazolyl
-O-
z =
4-Me-5-I-2-thiazolyl
4-Me-5-CN-2-thiazolyl
-o-
z =
4-Me-5-CF 3 -2-thiazolyI
WO 99/28305
PCT/US98/24265
82
Y
Column 1
Column 2
-O-
Z =
3-(HC=C)-phenyl
3-(CH 3 C=C)-phenyl
-O-
Z =
3-((CH 3 ) 3 CC=C)-phenyI
3-((CH 3 ) 3 SiC=C)-phenyl
-O-
Z =
3-(£>-0=C)-phenyl
5-Me-2-thienyl
-O-
Z =
5-(CH 3 ) 3 C-2-thicnyl
5-Cl-2-thienvl
-O-
Z =
5-Br-2-thienyl
5-I-2-thienyl
-O-
Z =
4-Me-2-thienyl
-O-
Z =
4-Cl-2-thienyl
4-Br-2-thienvl
-0-
Z =
4-I-2-thienyI
-O-
Z =
4-Me-5-Cl-2-thienyl
4-Me-5-Br-2-thienvl
-o-
Z =
4-Me-5-I-2-thienyl
3-C*l-2-thi<*nvl
-o-
Z =
5-Me-3-thienyl
j ^nj^ ^-j-uiicnyi
-o-
Z =
5-Cl-3-thienyl
5 - B r- 3 -th i en vl
-o-
Z =
5-I-3-thienyl
-o-
Z =
4-(CH 3 ) 3 C-3-thienyl
-o-
Z =
4-Br-3-thienyl
4-1-3 -thi en vl
* a — * uiiwiiy i
-o-
Z =
4,5-diMe-3-thienyl
4-Me-5-Cl-3-thipnvl
-o-
z =
4-Me-5-Br-3-thienyl
4-Me-5 -1-3 -thienvl
-o-
z =
2-Cl-3-thienyl
2-CF-5 -nhenvt
-CH 2 0-
z =
Phenyl
3-CF->-nhenv1
-CH 2 0-
z =
2-Me-5-/-Pr-phenyl
2-Me-4-OCH-> -nhenvl
-CH 2 0-
z =
4-OCF 3 -phenyl
2-Me-5-CF-j -Dhenvl
-CH 2 0-
z =
3-OCHF 2 -phenyl
4-OCHF 2 -phenyl
-CH 2 0-
z =
3,5-di(CF 3 )-phenyl
2-Me-4-OCHF-)-nhenv1
-CH 2 0-
z =
6-CF'3-2-pyridinyl
3-OCF^-nhenvl
-CH 2 0-
z =
4-CF 3 -2-pyridinyl
4-Me-2-Dvridinvl
« 1TXV *r p^UUUljl
-CH 2 0-
z =
2-Me-4-OCF 3 -phenyl
5-Me-2-nvridinvl
a* yJ j A Hill I y 1
-CH 2 0-
z =
3,6-diMe-2-pyridinyl
5 -CF -a -2 -d vridinvl
-CH 2 0-
z =
4,6-diMe-2-pyridinyl
n-Ol'F'^ -T)VT"iH i n\/l
-CH 2 0-
z =
4-CF 3 -6-Me-2-pyridinyI
3 -Me-2-n vridinvl
-CH 2 0-
z =
4-Cl-2-pyrimidinyl
o — Mi* <_ / _ irvri rl i n i / 1
\j x yic x. y i iu 11 1 y i
-CH 2 0-
z =
4-Cl-2-pyrimidinyl
3-Et-phenyl
-CH 2 0-
z =
2,6-diMe-4-pyridinyl
2,4,6-triMe-phenyl
-CH 2 0-
z =
3-Cl-2-pyridinyl
6-Cl-4-pyrimidinyl
-CH 2 0-
z =
1-napthalenyl
2,3,6-triMe-phenyl
-CH 2 0-
z =
6-Cl-2-pyrazinyl
4-CF 3 -2-pyrimidinyl
-CH 2 0-
z =
6-CF 3 -4-pyrimidinyl
2-/-Pr-phenyl
WO 99/28305
PCT/US98/24265
83
Y
Column 1
v^uiuimi z.
-CH 2 0-
Z =
3-Me-2-pyridinyl
-OCH 2 -
Z =
2-Me-phenyl
■^■j j™uiJiVic~piiciiyi
-OCH 2 -
Z =
3-CF 3 -phenyl
4-CF3-phenyl
-OCH 2 -
Z =
4-Me-phenyl
4— /-Rn-nhpnvl
-OCH 2 -
Z-
3-CI-phenyl
H-^i-pnenyi
-OCHo-
z =
o-f-DU-pnenyl
-OCH 2 -
Z =
2-naphthalenyl
i -napninaienyi
-OCHo-
Z =
3-nvriditivl
4-pyndinyl
-OCH 2 -
Z =
6-Me-2-r>vridinv1
leiranyaro jnapntnalenyl
-CH 2 0-N=C(CH 3 )-
z =
3-Nle-phenyl
H--\-,r ^ -pnenyi
-CH 2 0-N=C(CH 3 )-
Z =
3 5-di\'T(*-nhf*nv1
j-L,i-pnenyl
-CH 2 0-N=C(CH 3 )-
Z =
4-Br-nhetwl
o , d -ai(Cr 3)-pnenyl
-CH 2 0-N=C(CH 3 V
Z =
4-OCHF-i-nhpnvl
4-*-Bu-phenyl
-CH 2 0-N=C(CH 3 >
Z =
3-/-Bu-nhenv1
3-z-pynflinyi
-CH 2 0-N=C(CH 3 )-
Z =
4-OCF^> -nhenvl
j -vj Urlr 2 -pneny 1
-CH 2 0-N=C(CH 3 )-
Z =
S-Nfe-S-nvridinvl
^t-v-r 3 -o-JYic-z-pyriuiflyl
-CH 2 0-N=C(CH 3 )-
Z =
4-Me-2 -pyridinyl
*t , u - uiivic ~z - pyrioiiiyi
-CH 2 0-N=C(CH 3 )-
Z =
6-Tvfe -9-nvri H i n v 1
»-» «> L/y ii.u.iiiy i
o-t^r 3 -z-pyncunyi
-CH 2 0-N=C(CH 3 )-
Z =
6-OMe-2-pyridinyl
2,6-diMe-4-pyridinyl
-CH 2 0-N=C(CH 3 )-
z =
2.6-diCl-4-nvridinvl
j- vjv^r 3 -z-pynamyi
-CH 2 0-N=C(CH 3 )-
z -
4-OMe-2-Dvridinvl
t-vjv^F^-z-pynauiyi
-CH 2 0-N=C(CH 3 )-
z =
5-OCHF^-2-DvridiTivl
o-wv--rj-z-pyrjaiiiyi
-CH 2 0-N=C(CH 3 )-
z =
4-OCHF2-pyridinyl
j'yL-ri uniu ^pnenyi
-CH 2 0-N=C(CH 3 )-
z =
6-OCHF2-2-pyridinyl
j—Xj^jJiiciiyi
-CH 2 0-N=C(CH 3 )-
z =
1 -naphthalenyl
1 j,*+-TeTranyaro-z-
-CH 2 0-N=C(CH 3 )-
z =
3-SMe-phenyl
j-euiynyipncnyi
-CH 2 0-N=C(CH 3 )-
z =
t-Bu
^c~r - j - v^r* 3 -pnenyi
-CH=N-OCH(CH 3 )-
z =
4-CF?-Dhenvl
3-CF3 -phenyl
-CH=N-OCH(CH 3 ) :
z =
4-OCF 3 -phenyl
3-OCF-a-ohenvl
-CH=N-OCH(CH 3 )-
z =
3-Cl-phenyl
4-Cl-phenyl
-CH=N-OCH(CH 3 )-
z =
3,5-diCl-phenyl
3,5-di(CF 3 )-phenyl
-CH=N-OCH(CH 3 )-
z =
3-Me-phenyl
4-Me-phenyl
-CH=N-OCH(CH 3 )-
z =
2-naphthalenyl
4-OCHF 2 -phenyl
-CH=N-OCH(CH 3 )-
z =
3-OCHF 2 -phenyl
4-CF 3 -2-pyridinyl
-CH=N-OCH(CH 3 )-
Z - | 5-CF 3 -2-pyridinyl
6-CF 3 -2-pyridinyl
WO 99/28305
PCT/US98/24265
84
Y
Pnlnmn 1
column 2
-CH=N-OCH(CH 3 )-
T-
4-lVle -2 -nvri di n vl
5-Me-2 -pyridinyl
-CH=N-OCH(CH 3 )-
Z =
6-^4e-2-nvridinvI
v *»*V |*J ' Mill IV I
^-L-r^-o-JYie-x-pynainyl
-CH=N-OCH(CH 3 )-
z =
5-OCF3 -2-pynainy 1
-CH=N-OCH(CH 3 )-
Z =
6-OCF-3 -2-Dvridinvl
H-\j\^tir 2"^-'Pynuinyi
-CH=N-OCH(CH 3 )-
z =
vjwxix*2 ^ pyriuinyi
6-CJCHF2"2-pynaiiiyl
-CH=N-OCH(CH 3 )-
Z =
3 -/-Bu-nhenvl
4-/-Bu-phenyl
-CH 2 -SC(Et)=N-
Z =
4— CTF-> -nhf*nvl
3-Cr3-pnenyl
-CH 2 -SC(Et)=N-
z =
' vvi 3 piiciiyi
3-OCF 3 -phenyl
-CH 2 -SC(Et)=N-
z =
pucny l
4-Cl-phenyl
-CH 2 -SC(Et)=N-
z =
1 S-diPl_nh£»r»\/1
3,5-di(CF 3 )-phenyl
-CH 2 -SC(Et)=N-
z =
j ivic-pucnyi
4-Me-phenyl
-CH 2 -SC(Et)=N-
z =
S— Hi N/f f*— n n*»m/l
- J i~' uiivi.c~|^iiciiyi
2-naphthalenyl
-CH 2 -SC(Et)=N-
z =
u-ivic-z-pynaiiiyi
4-Me-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
4 ^-HiTv/ff-^-rwrriHim/l
*ju.vj.c-x. _ pynuiiiyi
5-CI-2-pyndinyl
-CH 2 -SC(Et)=N-
z =
**, o-uiv^i -z-pynainy l
5-Me-2 -pyridinyl
-CH 2 -SC(Et)=N-
z =
5-Br-6-Me-2-pyndinyl
-CH 2 -SC(=S)NMe-
z =
4— i P-i -nnpnvl
3-CF 3 -phenyl
-CH 2 -SC(=S)NMe-
z =
J-OCl , 3 -pnenyl
-CH 2 -SC(=S)NMe-
z =
3-Cl-nhenvl
H-oi-pnenyi
-CH 2 -SC(=S)NMe-
z =
3 5-diCl-nhenvl
J,5-ai(Cr 3 )-pnenyl
-CH 2 -SC(=S)NMe-
z =
J J.VJ.f |JllWil Y 1
4-Me-phenyl
-CH 2 -SC(=S)NMe-
z =
S-dl\/f (=»»r*li*»n\/1
— 's-* uiivic-pucuy l
2-naphthalenyl
-CH 2 -SC(=S)NMe-
z =
v ^> ^syiiumyj
4-Me-2-pyridinyl
-CH 2 -SC(=S)NMe-
z =
4 6-diA4e-'?-nvridinv1
j-t-i-z-pyndinyl
-CH 2 -SC(=S)NMe-
z =
4.6-diCl-2-nvridinvl
5-Me-2-pyridinyl
-CH 2 -SC(=S)NMe-
z =
5-C>Ft TYV/TlHinvl
■* j a> \J y a iuiii y i
j-rsr-o-ivie-z-pynclinyl
-CH 2 SC(SMe)=N-
z =
3-Me-nhenvl
4-Me-phenyl
-CH 2 SC(SMe)=N-
z =
*a S— di Arff*— nhAnirl
«-'>-' *-iiivic~pnciiyi
3-Cl-pnenyl
-CH 2 SC(SMe)=N-
z -
4-Cl-nhenvl
->,j-uid-prienyl
-CH 2 SC(SMe)=N-
z =
^ _ i P .nnpnul
v^-i T~puciiyi
4-ur 3 -phenyl
-CH 2 SC(SMe)=N-
z =
3-OCF 3 -phenyl
4-OCFi-nhenvl
-CH 2 SC(SMe)=N-
z =
3,5-di(CF 3 )-phenyl
CH 2 CH 2 -<-Bu
-CH 2 SC(SMe)=N-
z =
/-Bu
2-naphthalenyl
-CH 2 SC(SMe)=N-
z =
6-Me-2-pyridinyl
4-Me-2 -pyridinyl
-CH 2 SC(SMe)=N-
z =
4,6-diMe-2-pyridinyl
5-Cl-2-pyridinyl
-CH 2 SC(SMe)=N-
z =
4, 6-diCl-2-pyridiny I
5-Me-2-pyridinyl
-CH 2 SC(SMe)=N-
z =
5-CF 3 -2-pyridinyl
5-Br-6-Me-2-pyridinyl
WO 99/28305
PCT/US98/24265
85
Y
Column 1
Pnlnmn 9
-CH 2 S-
Z =
2-Me-nhenvl
j -L, r ^ -pneny l
-CH 2 S-
Z =
-nhpnvl
-c,D-oiMe-pnenyl
-CH 2 S-
z =
2-Et-nhenvl
j-i^i-pnenyi
-CH 2 S-
z =
2-Cl-nhenvl
2,5-aiCi-pnenyI
-CH 2 S-
Z =
Uliviw A> ^-/jr 1 lUUUUly I
i-Me- 1 ,z,4-tnazol-3-yl
-CH 2 S-
z =
*» iit*pilU.laivJJjrl
1 -Me-2 -lmidazolyl
-CH 2 S-
z =
*t ivic~z-pyixniiaiiiyi
5-Me- 1 ,3,4-thiadiazol-2-yl
-CH 2 0-N=C(CH-j)CH->S-
z =
J ivic— piiciiyi
2-Me-phenyl
-CH 2 0-N=C(CH?)CH 9 S-
z =
«■* -T t -p jienyi
4-CF 3 -phenyl
-CH 2 0-N=C(CH^)CH 9 S-
z -
^-Pl-ntiArrul
v_*i-pjiciiyi
2-Et-phenyl
-CH 2 0-N=C(CH-i)CHoS-
z =
*▼ v^i-jjijciiyi
2-naphthalenyl
-CH 2 ON=C(CH 3 )CH 2 S-
z =
a.,^ uiivic~piiciiyi
4-CF 3 -2-pyridinyl
-CH 2 0-N=C(CH*)CH->0-
z =
-* itjlv piiciiy A
2-Me-phenyl
-CH 2 0-N=C(CH-j)CH->0-
z =
4— A^^—i"* Vi pm; 1
~ ivie-piiciiy 1
3-CF 3 -phenyI
-CH 2 O-N=C(CH3)CH 2 0-
*• v -5-' X
z =
4-PF -nhpm/l
4-Cl-phenyl
-CH 2 O-N=C(CH 3 )CH 2 0-
z =
3-Cl-ohenvl
3,D-diMe-pnenyl
-CH 2 0-N=C<CH 3 )CH 2 0-
z =
2 5-dilW[e-nhenvl
z-Me-D-z-ir-pnenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
3-Et-phenyl
o-^r 3 -z-pynumyj
-CH 2 0-N=C(CH 3 )CH 2 O-
z =
■ V -' A J fJjrllUUlyl
D-Cr 3-2-pynainy]
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
6-Me-2 -pyridiny I
5 -Ms -2 -pyndiny 1
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4-Me-2 -pyridiny 1
i -napninaienyi
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
2-nanhfhfllpnvl
z-(_.r 3 -pnenyl
-CH 2 CH 2 -
z =
2-Me-ohenvl
2,5-diMe-phenyI
-CH 2 CH 2 -
z =
3-CF^ -nhenvl
3 -pnenyl
-CH 2 CH 2 -
z =
3-CI-phenyl
fc f-v_.i-piicnyi
-CH 2 CH 2 -
z =
3 -OCF*j -Dhenvl
H-vj^r 3 -pnenyi
-CH 2 CH 2 -
z =
2-Et-phenyl
^-me-j-vi-pnenyi
-CH 2 CH 2 -
z =
2-naohthalenvl
3,6-diMe-2-pyridinyl
-CH=C(CH 3 )-
z =
3 -IVIe-r>Vi pn vl
— ' «iv i/iiviiy i
4-Me-phenyl
-CH=C(CH 3 )-
z =
3 S-Hi N/f f^-rth^nvl
j-Cl-pnenyl
-CH=C(CH 3 )-
z =
4-Cl-phenyl
3-OCF 3 -phenyl
-CH=C(CH 3 )-
z =
4-OCF 3 -phenyl
3-CF 3 -phenyl
-CH=C(CH 3 )-
z =
4-CF 3 -phenyl
2-naphthalenyl
-CH=C(CH 3 >
z =
4-CF 3 -2-pyridinyl
6-CF 3 -2-pyridinyl
-CH=N-N=C(CH 3 )-
z =
3-Me-phenyl
4-Me-phenyl
-CH=N-N=C(CH 3 )-
z =
3-CF 3 -phenyl
4-CF 3 -phenyl
-CH=N-N=C(CH 3 )-
z =
3-OCF 3 -phenyl
4-OCF 3 -phenyl
WO 99/28305
PCT/US98/24265
86
Y
Column 1
v^oiunxn z
-CH=N-N=C(CH 3 )-
z =
3-Cl-pnenyl
-CH=N-N=C(CH 3 )-
z =
4-Cl-nhenvl
3 ,5-diCl-pnenyI
-CH=N-N=C(CH 3 )-
Z =
4-CF*}->2-TwriHiTi\/l
o-Ur 3 -2-pyndinyl
-CH=N-N=C(CH 3 )-
Z =
o-CF"5-2-TYvriHiTiv1
4-Me-2-pyridinyl
-CH=N-N=C(CH 3 )-
z =
5-Me-2-twridinvl
6-Me-2-pyridinyl
-CH=N-N=C(CH 3 )-
z =
2-nanhtha Ipnvl
4,6-diMe-2-pyndinyl
-CH=N-N=C(CH 3 )-
z =
^ -F f-r*h priv/1
t-Bu
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
3-Me-nhenvl
4-Me-phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
3-Cl-phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
4-CI-nhenvl
3,5-diCl-phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
Z =
3-CF-5-nh**nv1
4-Cr 3 -phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
3 5-difCF^ Wihwivl
i-U(_r 3 -phenyI
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-OCFi-nhenvl
CH 3
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
/-Bu
O t__ - l__ 1 «
2-naphthalenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-/-Rn-nh<*m/1
4-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
5-Me-2-nvriHinvl
6-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-CF3-2-pyridinyl
3-\^r ^-z-pynainyi
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
6-CF3 -2-pyri diny 1
4,6- diMe-2-pyndinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-CFo-2-nvrirnidinvl
6-CF3 -2-pyrimidiny 1
-CH=N-N(CH 3 )-
z =
3-Me-phenyl
4-Me-phenyl
-CH=N-N(CH 3 )-
z =
3,5-diMe-phenyl
j -^-j-pnenyi
-CH=N-N(CH 3 )-
z =
4-Cl-phenyl
^ S rlir^l nliomrl
0 , j -ui\_yi-pnenyi
-CH=N-N(CH 3 >
z =
3-CFa-ohcnvl
^•wr^-pnenyi
-CH=N-N(CH 3 >
z =
3-OCF^-ohenvI
^•utr 3 -pnenyi
-CH=N-N(CH 3 )-
z =
2-naphthalenyl
H-i -iju-p neny i
-CH=N-N(CH 3 )-
z =
4-Me-2-twt*iHinvl
3-Me-2-pyndinyl
-CH=N-N(CH 3 )-
z =
6-^4e-2-nvridinv1
3 -2-pynainyl
-CH=N-N(CH 3 )-
z =
5-CF*2 -2-nvridinvl
o-L-r 3 -z-pynainyl
-CH=N-N(CH 3 )-
z =
4 fi-diX^P-^-TWriHiirwl
4-CF 3 -2-pyrimidinyl
-CH 2 0C(SMe)=N-
z =
4-CFo-nhenvl
3-Cr 3 -pnenyl
-CH 2 OC(SMe)=N-
z =
4-OCF 3 -phenyl
j v^v-/F 3 -pnenyi
-CH 2 OC(SMe)=N-
z =
3-Cl-phenyl
4-Cl-phenyl
-CH 2 OC(SMe)=N-
z =
3,5-diCl-phenyl
3-Me-phenyl
-CH 2 OC(SMe)=N-
z =
4-Me-phenyl
3,5-diMe-phenyl
-CH 2 OC(SMe)=N-
z =
2-naphthalenyl
6-Me-2-pyridinyl
-CH 2 OC(SMe)=N-
z =
4-Me-2-pyridinyl
4,6-diMe-2-pyridinyl
-CH 2 OC(SMe)=N-
z =
5-CF 3 -2-pyridinyl
5-Me-2-pyridinyl
WO 99/28305
PCT/US98/24265
87
Y
• Column 1
Column 2
-CH 2 OC(=S)NMe-
Z =
4— C P -> — h P nvl
« "J— JJlICIlj'l
3-CF3-phenyl
-CH 2 OC(=S)NMe-
Z =
4-OCF3 -phenyl
•j-u^r^-pnenyi
-CH 2 OC(=S)NMe-
Z =
3-Cl-phenyl
*t-\^ i-pneny 1
-CH 2 OC(=S)NMe-
z =
3,5-diCl-phenyl
3 -Me-pheny 1
-CH 2 OC(=S)NMe-
z =
4-\f e-r>h pnvl
3,5-duMe-phenyl
-CH 2 OC(=S)NMe-
z =
2-nanhthalpnvl
6-Me-2-pyridinyl
-CH 2 OC(=S)NMe-
z =
4-N/f e-2-nvri(i i n vl
4,o-aiMe-2-pyndinyl
-CH 2 OC(=S)NMe-
z =
5-CF-a -2-DvriHinvl
5-Me-2-pyridinyl ,
-SCH 2 -
z =
2-Me-phenyl
2,5-diMe-phenyl
-SCH 2 -
z =
3-CF3-phenyl
4-CKo -nhenvl
-SCH 2 -
z =
4-Me-nh envl
4-f-Bu-phenyl
-SCH 2 -
z =
3-Cl-nherivl
4-Cl-phenyl
-SCH 2 -
z =
2-Me-^-PI-nhpnvl
^ ivic-»j-v^i-pnciiyi
3-f-Bu-phenyl
-SCH->-
z =
/•nQnntnalam pi
X"iidpxiixmienyi
1-naphthalenyl
-SCH^-
z -
3 -pynainy i
4-pyridinyl
-SCH 2 -
z =
u ivj.c-^-pynuinyi
5,6,7,8-tetrahydro-2-
naphthalenyl
-CH 2 0-N=C(SCH 3 )-
z -
-> \~>i 3 piicnyi
3-OCF 3 -phenyl
-CH 2 0-N=C(SCH 3 )-
Z-
p-nh pti vl
4-Cr 3 -phenyI
-CH 2 0-N=C(SCH 3 )-
z =
4-OCF 3 -phenyl
4-Me-phenyl
-CH 2 0-N=C(SCH?)-
z =
j-^i-pnenyi
3,5-diCl-phenyl
-CH 2 0-N=C(cyclopropyl)-
z =
3 -CF 3 -phenyl
j-ui^r 3 -pnenyl
-CH 2 0-N=C(cyclopropyl)-
z =
3-Me-phenyl
't-L-r 3 -pnenyi
-CH 2 0-N=C(cyclopropyl)-
z =
4-OCF 3 -phenyl
4-Me-phenyl
-CH 2 0-N=C(cyclopropyl)-
z =
3-Cl-phenyl
3,5-diCl-phenyl
Table 4b
= C1
Y
Column 1
O ril 1 1 ti 1 ri *>
-O-
z =
Phenyl
3-OMe-phenyl
-O-
z =
4-CF 3 -phenyl
3-Me-phenyl
-O-
z =
3-F-phenyl
3-OCF 3 -phenyl
-O-
z -
4-Me-phenyl
3-I-phenyl
-O-
z =
3-SCH 3 -phenyl
2-Me-phenyl
-O-
z =
3-SCHF 2 -phenyl
4-SCH 3 -phenyl
-O-
z =
3-cyclohexyl-phenyl
4-SCHF 2 -phenyl
WO 99/28305
PCT/US98/24265
88
Y
Column 1
Column 2
-O-
z =
6-CF3-2-pyridinyl
5-CF 3 -2-pyridinyl
-O-
z =
4-CF 3 -2-pyridinyl
6-Mc-2-pyridinyl
-O-
z =
6-(CF3CH 2 0)-4-pyrimidinyl
5-Me-2-pyridinyl
-O-
z =
2-(CF 3 CH20)-4-pyrimidinyl
4-(CF-jCH-)OV2-Dvrimidinvl
-O-
z =
4-Me-2-pyridinyl
3 5-diM^G-nhenvl
-0-
7, =
2-naphthalenyl
5,6,7,8-tetrahydro-2-
nanhthalenvl
-O-
z~
4-OCF 3 -phenyl
3 -/-B u-pheny 1
-o-
z =
4-f-Bu-phenyl
6-CCF'aCHoOV2-nvra7inv1
-o-
z =
3-SCF 3 -phenyl
-o-
z =
4-CF 3 -6-Me-2-pyridinyl
-o-
z =
4,6-diMe-2-pyridinyl
-o-
z =
5-Cl-2-thiazolyl
5-I-2-thiazolvl
-o-
z =
5-OCF 3 -2-thiazolyl
-o-
z =
5-CN-2-thiazolyl
5-SCH 3 -2-thiazolyl
-o-
z =
5-CF 3 -2-thiazolyl
4-Me-5-Cl-2-thiazolyl
-O-
z =
4-Me-5-I-2-thiazolyl
4-Me-5-CN-2-thiazolyl
-o-
z =
4-Me-5-CF 3 -2-thiazolyl
-o-
z =
3-(HQ=Q-phenyl
3-(CH 3 OC)-phenyl
-o-
z =
3-((CH 3 ) 3 CC=C)-phenyl
3-((CH 3 ) 3 SiC=C)-phenyl
-o-
z =
3-( [>-C=Q-phenyl
5-Me-2-thienyl
-o-
z =
5-(CH 3 ) 3 C-2-thienyl
5-Cl-2-thienyl
-o-
z =
5-Br-2-thienyl
5-I-2-thienyl
-O-
z =
4-Me-2-thienyl
4-(CH 3 ) 3 C-2-thienyl
-o-
z =
4-Cl-2-thienyl
4-Br-2-thienyl
-0-
z =
4-I-2-thienyl
4,5-diMe-2-thienyl
-o-
z =
4-Me-5-Cl-2-thienyl
4-Me-5-Br-2-thienyl
-o-
z =
4-Me-5-I-2-thienyl
3-Cl-2-thienyl
-o-
z =
5-Me-3-thienyl
5-fCH^1-> P-^-thipnvl
-o-
z =
5-Cl-3-thienyI
5-Br-3-thienyl
-o-
z =
5-I-3-thienyl
4-Me-3-thienyl
-o-
z =
4-(CH 3 ) 3 C-3-thienyl
4-Cl-3-thienyl
-o-
z =
4-Br-3-thienyl
4-I-3-thienyl
-o-
z =
4,5-diMe-3-thienyl
4-Me-5-Cl-3-thienyl
-O-
z =
4-Me-5-Br-3-thienyl
4-Me-5-I-3-thienyl
-o-
z =
2-Cl-3-thieny1
2-CF 3 -phenyl
WO 99/28305
PCT/US98/24265
89
Y
Column 1
Column 2
-CH 2 0-
Z =
Phenyl
3-CF 3 -pnenyl
-CH 2 0-
Z =
2-Me-5-j"-Pr-phenyl
2-Me-4-OCH 3 -phenyl
-CH 2 0-
Z =
4-OCF 3 -phenyl
2-Me-5-CF 3 -phenyl
-CH 2 0-
Z =
3-OCHF 2 -phenyl
4-OCHF 2 -phenyl
-CH 2 0-
Z =
3,5-di(CF 3 )-phenyl
2-Me-4-OCHF 2 -phenyl
-CH 2 0-
Z =
6-CF 3 -2-pyridinyl
3-OCF 3 -phenyl
-CH 2 0-
Z =
4-CF 3 -2-pyridinyl
4-Me-2-pyridinyl
-CH 2 0-
Z =
2-Me-4-OCF 3 -phenyl
5-Me-2-pyridinyl
-CH 2 0-
z =
3,6-diMe-2-pyridinyl
5-CF 3 -2-pyridinyl
-CH 2 0-
z =
4.6-diMe-2-ovridinvl
6-OCF 3 -2-pyridinyl
-CH 2 0-
z =
4-CF3-6-Me-2-pyridinyl
3-Me-2-pyridinyl
-CH 2 0-
z =
4-Cl-2-Dvrimidinvl
6-Me-2-pyridinyl
-CH 2 0-
z =
4-C 1-2 -nvrim idin vl
3-Et-phenyl
-CH 2 0-
z =
2.6-diMe-4-Dvridinvl
2,4,6-triMe-phenyl
-CH 2 0-
z =
3-Cl-2-pyridinyl
6-Cl-4-pyrimidinyl
-CH 2 0-
z =
1 -napthalenyl
2,3,6-triMe-phenyl
-CH 2 0-
z =
6-Cl-2-pyrazinyl
4-CF 3 -2-pyrimidinyl
-CH 2 0-
z =
6-CF 3 -4-pyrimidinyl
2-i*-Pr-phenyl
-CH 2 0-
z =
3-Me-2-pyridinyl
4-Cl-2-pyridinyl
-OCH 2 -
z =
2-Me-phenyl
2,5-diMe-phenyl
-OCH 2 -
z =
3-CF 3 -phenyl
4-CF 3 -phenyl
-OCH 2 -
z =
4-Me-phenyl
4-r-Bu-phenyl
-OCH 2 -
z =
3-Cl-phenyl
4-Cl-phenyl
-OCH 2 -
z =
2-Me-5-Cl-phenyl
3-f-Bu-phenyl
-OCH 2 -
z =
2-naphthalenyl
1-naphthalenyl
-OCH 2 -
z =
3-pyridinyl
4-pyridinyl
-OCH 2 -
z =
6-Me-2-pyridinyl
2-(5,6,7,8-
tetrahydro)naphthalenyl
-CH 2 0-N=C(CH 3 )-
z =
3-Me-r>henvl
4-CF 3 -phenyl
-CH 2 0-N=C(CH 3 )-
z =
3 5-diN/fe-T>hetivl
j-^i-pjienyi
-CH 2 0-N=C(CH 3 )-
z =
4-Br-phenyl
3,5-di(CF 3 )-phenyl
-CH 2 0-N=C(CH 3 )-
z =
4-OCHF 2 -phenyl
4-r-Bu-phenyl
-CH 2 0-N=C(CH 3 )-
z =
3-/-Bu-phenyl
5-CF 3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )-
z =
4-OCF 3 -phenyl
3-OCHF 2 -phenyl
-CH 2 0-N=C(CH 3 )-
z =
5-Me-2-pyridinyl
4-CF 3 -6-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )-
z =
4-Me-2-pyridinyl
4,6-diMe-2-pyridinyl
-CH 2 0-N=C(CH 3 )-
z =
6-Me-2-pyridinyl
6-CF3 -2-pyridinyl
WO 99/28305
PCT/US98/24265
90
Y
Column 1
V_< Ul UIIU1 J.
-CH 2 0-N=C(CH 3 )-
Z =
6-OMe-2-pyridinyl
2,6-diMe-4-pyridinyl
-CH 2 0-N=C(CH 3 )-
Z =
2,6-diCl-4-pyridinyl
j vA/ r j -,^-py riuiuy i
-CH 2 0-N=C(CH 3 )-
Z =
4-OMe-2-Dvridinvl
t"uv_.r 3 ^ pyriciinyi
-CH 2 0-N=C(CHo)-
Z. \ J/
Z =
5 - Cj ll HF ^» — V — r* vri H i nv 1
O-ULr 3-z-pyriuinyi
-CH 2 0-N=C(CH 3 )-
z =
4-OCHFt -Dvridinvl
j-l k Lr^Ln2U jpnenyi
-CH 2 0-N=C(CH 3 )-
z =
6-OCHF-) -2-Dvridinvl
j -nc-pnenyj
-CH 2 0-N=C(CH^)-
z =
1 -nanhthnlpnvl
1,2,3 ,4-tetranydro-2-
napninaicnyi
-CH 2 0-N=C(CH^)-
z =
^ - RA^p— t\ h f»tr\rl
— ' uivic pii^ilY 1
3-ethynylphenyl
-CH 2 0-N=C(CH 3 >
z =
<-Bu
O 17 C /"'IT nV>am>l
■£-r 0-i»,r 3-pneny]
-CH=N-OCH(CH,)-
z =
4-CF-j-nhenvl
^-^r3-pnenyl
-CH=N-OCH(CH 3 )-
z =
4-OCF-> -nhenvl
3 -phenyl
-CH=N-OCH(CH 3 )-
z =
3-Cl-nhenv1
^-Cl-pnenyl
-CH=N-OCH(CH^V
z =
3.5-diCl-nhenvl
jjj-am^r^^-pnenyi
-CH=N-OCH(CHo)-
z =
3-Me-nhenvJ
4-Me-phenyl
-CH=N-OCH(CH^)-
z =
2-naphthalenyl
H-\^^xijr2~pnenyi
-CH=N-OCH(CH 3 )-
z =
3-OCHFo-ohenvl
-2-pyndiny 1
-CH=N-OCH(CH^)-
z =
5-CKo -2-trvririiTivI
o-cr 3 -z-pynainyl
-CH=N-OCH(CHa)-
z =
4-Me-2-pyridinyl
i vie - z py n uiny i
-CH=N-OCH(CH 3 )-
z =
6-lMe-2-pyridinyl
*t-v_-x'3 o -ivic-x-pyriQiiiyi
-CH=N-OCH(CH,)-
z =
4-0(TFo -?-nvridinv1
j-uLr^ -z-pynainyi
-CH=N-OCH(CH 3 )-
z-
6-OCF 3 -2-pyridinyl
" -xy\^xTj*9 *• pynoinyi
-CH=N-OCH(CH*)-
z =
5-OCHF^-2-iwriHiTivl
o-^\^jxr2"^"pynoinyi
-CH=N-OCH(CH^)-
z =
3-<-Bu-phenyl
A m. t— ¥5 11 V» am /I
*T""i - j_>Q-uiiciiy 1
-CH 2 -SC(Et)=N-
z =
4-CF 3 -phenyl
-CH 2 -SC(Et)=N-
z =
4-OCF 3 -phenyl
^ ,nh (»ti vl
j "v-/^w jt *3 -piiciiy 1
-CH 2 -SC(Et)=N-
z =
3-Cl-phenyl
" v^t jjiiciiy i
-CH 2 -SC(Et)=N-
z =
3,5-diCl-phenyl
-CH 2 -SC(Et)=N-
z =
3-Me-phenyl
A A4q .nnotn/l
*f~ivi c-piiciJi.y i
-CH 2 -SC(Et)=N-
z =
"\ S - H i \A p— nhi*nvl
2-naphthalenyl
-CH 2 -SC(Et)=N-
z =
6-Me-2-pyridinyl
4-Me-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
4,6-diMe-2-pyridinyl
5-Cl-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
4,6-diCl-2-pyridinyl
5-Me-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
5 -CF 3 -2-pyridinyl
5-Br-6-Me-2-pyridinyl
-CH 2 -SC(=S)NMe-
z =
4-CF 3 -phenyl
3 -CF3 -phenyl
-CH 2 -SC(=S)NMe-
z =
4-OCF 3 -phenyl
3-OCF 3 -phenyl
-CH 2 -SC(=S)NMe-
z =
3-Cl-phenyl
4-Cl-phenyl
WO 99/28305
PCT/US98/24265
91
Y
Pnliimn 1
Column 2
-CH 2 -SC(=S)NMe-
2 =
3 ,5 -di(CF 3 )-pheny 1
-CH 2 -SC(=S)NMe-
7 =
3 ~M c -phenyl
4-Me-phenyl
-CH?-SCr=S')NMe-
j,j-uijvie-pncnyi
2-naphthalenyl
-CH->-SC(=S)NMe-
A, —
6-Me -2-py ridiny 1
4-Me-2-pyridinyl
-CH 2 -SC(=S)NMe-
2 =
h, o-uiivic-^-pyrioiiiy i
5-Cl-2-pyridinyl
-CH 2 -SC(=S)NMe-
2 =
">\j-uiv_,i-z~pynuiiiyi
5-Me-2-pyndinyl
-CH 2 -SC(=S)NMe-
5-CF^-2-pyndinyl
5-Br-6-Me-2-pyridinyl
-CH 2 SC(SMe)=N-
7 =
3 -Mc-pheny 1
4-Me-phenyl
-CH 2 SC(SMe)=N-
7 —
3,5-diMe-phenyl
3-Cl-phenyl
-CH 2 SC(SMe)=N-
7 _ :
4-C1 -phenyl
3,5-diCl-phenyl
-CHoSCfSMe^N-
7 =
^-L^r 3 -pnenyl
4-CF 3 -phenyl
-CH 2 SC(SMe)=N-
2 =
j-uvri -pnenyi
4-OCF 3 -phenyl
-CH 2 SC(SMe)=N-
2 =
/ 'TT pu y~\. .
CH2CH2-M5U
-CH 2 SC(SMe)=N-
2 -
/-Rn
2-naphthalenyl
-CH 2 SC(SMe)=N-
2 =
o-ivic-jc-pynainyi
4-Me-2-pyndmyl
-CH 2 SC(SMe)=N-
2 =
*t, u-ujjvie-z-pyriuiny 1
5-Cl-2-pyridinyl
-CH 2 SC(SMe)=N-
2 =
~t , u - ui i - z-py n tiiny l
5-Me-2-pyridinyl
-CH 2 SC(SMe)=N-
Z-
~* v^x 3 ^"pyiiiuiiy i
D-JBr-o-ivie-z-pynainyl
-CH 2 S-
7 =
2-Me-phenyl
3-CF 3 -phenyl
-CH^S-
7 —
H-ct^-pnenyi
2,5-diMe-phenyl
-CH 2 S-
2 =
z-ni-pnenyi
3-Cl-phenyl
-CH 2 S-
7 —
x-ci-pnenyl
2,5-diCl-phenyl
-CH 2 S-
7 =
4, 6-diMe-2-pyrimidiny 1
4-Me- 1 ,2,4-triazol-3-yl
-CH 2 S-
2 =
-t. "liapilUlolCQy 1
1 -Me-2-imidazolyl
-CH 2 S-
2 =
4-Me-2-pyrimidinyl
5-Me- l,3,4-thiadiazol-2-yl
-CH 2 0-N=C(CH 3 )CH 2 S-
2 =
o-ivie-pnenyi
2-Me-phenyl
-CH 2 0-N=C(CH 3 )CH 2 S-
2 =
j v^i , 3 -pnenyi
4-CF 3 -phenyl
-CHoO-N^fCH^ICHoS-
7 —
•5-v-i-pnenyi
2-Et-phenyl
-CHiO-N==C(CHilCHoS-
7 =
*r-L.i-pnenyi
2-naphthalenyl
-CH->0-N=C(CH^1CttiS-
7 —
2,5-diMe-phenyl
4-CF 3 -2-pyridinyl
-CHiO-N^QCH-OCHiO-
7 =
3-Me-phenyl
2-Me-phenyl
-CH 2 0-N=C(CH 3 )CH 2 O-
Z =
4-Me-phenyl
3-CF 3 -phenyl
-CH 2 0-N=C(CH 3 )CH 2 O-
Z =
4-CF 3 -phenyl
4-Cl-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
3-Cl-phenyl
3,5-diMe-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
2,5-diMe-phenyl
2-Me-5-/-Pr-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
3-Et-phenyl
6-CF 3 -2-pyridinyl
-CH 2 0-N=C{CH 3 )CH 2 0-
Z =
4-CF 3 -2-pyridinyl
5-CF 3 -2-pyridinyl
WO 99/28305
PCT/US98/24265
92
Y
Column 1
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
6-Me-2-pyridinyl
j-ivic-z-pyriaLuyi
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
4-Me-2-pyridinyl
1 tin rkntnnlanill
1 -napnuiiiiciiy 1
-CH 2 0-N=C(CH 3 )CH 2 O-
z =
2-naphthalenyl
z-v^r^-pnenyi
-CH 2 CH 2 -
z =
2-Me-nhenvl
2 ,5 -diMe-phenyl
-CH9CH9-
z =
3-CF-5 -nhenvl
4-CF^ -phenyl
-CH 2 CH 2 -
z =
3-Cl-phenyl
*t- i-pneny 1
-CH 2 CH 2 -
z =
S-OCF'j-Dhenvl
n-ULr 3 -pnenyi
-CH 2 CH 2 -
Z =
2-Et-nhenvl
z-Mc-D-d-pnenyi
-CH 2 CH->-
Z =
2-nanhthalenvl
3,6-diMe-2-pyndinyl
-CH=C(CH 3 )-
z =
^ — f* ~T\ H **n v 1
— ' piivuyi
4-Me-phenyl
-CH=C(CH,)-
z =
"5 pi _ i__ -..,1
3-ci-pnenyl
-CH=C(CH 3 )-
z =
4-C1 -nhenvl
i-utr 3 -pnenyi
-CH=C(CH 3 )-
z =
4-OPF'* -nhpnvl
3-CF 3 -pnenyl
-CH=C(CH?)-
z -
-nhpnvl
~ ^1 3 j-Hiciiyi
2-naphthalenyl
-CH=C(CH 3 )-
z =
4-CF-}-2-iwriHinvl
o-Lr 3 -^-pynainyl
-CH=N-N=C(CH 3 )-
z =
4-Me-phenyl
-CH=N-N=C(CH-»)-
z =
^— OF^ -Tl ViPTTY/1
3 IT J
4-Cr 3 -pnenyl
-CH=N-N=C(CH,)-
z =
3-OCF-* -nhenvl
W'-'r * jJiiviiyi
3 -pnenyi
-CH=N-N=C(CH 3 )-
z =
j, j -uiivie-pnenyi
3-Cl-phenyl
-CH=N-N=C(CH 3 >-
z =
4 -fl -n hf*TT\/l
~ V-'l pnenyi
jjj-aiUl-pnenyl
-CH=N-N=C(CH*)-
z =
4.iF"> — 7— nvr"i Hi n\/1
3 -2-pynainyl
-CH=N-N=C(CH?>
z =
\J V-'l 3 4- jjjr 1 ivjiuy 1
4-Me-2-pyridinyl
-CH=N-N=C(CH 3 )-
z =
5-Me-2-nvridinv1
6-Me-2-pyndinyl
-CH=N-N=C(CH 3 )-
z =
2-naphthalenyl
n,o-aiivie-z-pynuinyi
-CH=N-N=C(CH 3 )-
z =
3-Et-phenyl
/ Tin
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
3-Me-nhenvl
4-Me-phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH,)-
z =
3 5-diMe-nhenvl
j-i^i-pnenyi
-CH 2 0-N=C(CH 3 )C(=NOCH,)-
z =
4-OI-nhf»nv1
j,j-aii_i-pnenyi
-CH 2 0-N=C(CH 3 )C(=NOCH?)-
z =
^— (^Fi -nhpiivl
— * v_^-i j i/iiviiyi
4-CF 3 -phenyl
-CH 2 O-N=C(CH 3 )C(=N0CH 3 )-
z =
J-UCr 3 -pnenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-OCF 3 -phenyI
CH 3
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
/-Bu
2-naphthalenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-r-Bu-phenyl
4-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
5-Me-2-pyridinyl
6-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-CF3 -2-pyridinyl
5-CF 3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
6-CF3 -2-pyridinyl
4,6-diMe-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-CF3 -2-pyrimidinyl
6-CF 3 -2-pyrimidinyl
WO 99/28305
PCT/US98/24265
93
Y
Column 1
f"V*Inmri 0
I^UIUIILlI Z
-CH=N-N(CH 3 )-
Z =
3 envl
H-ivic -pncny i
-CH=N-N(CH 3 )-
Z =
3 5-diMe-nhenvl
■^.ri.nhpm/l
o-v^i-piiciiyi
-CH=N-N(CH 3 )-
z =
4-Cl-phenyl
j, j-uiv^-i-jjncxiyi
-CH=N-N(CH 3 )-
z =
3 -CF^ -phenyl
*t- v^.r 3 -pneny i
-CH=N-N(CH 3 )-
Z -
3-OCF-a -nhenvl
4 nPl?* nhonvl
*T-\j\^r 3-pnenyi
-CH=N-N(CH 3 )-
z =
4-?-_Bu-phcnyl
-CH=N-N(CH 3 )-
2 =
ivie-z -py nainy i
5-Me-2-pyridinyl
-CH=N-N(CH 3 )-
2 —
o-ivic-z -pyriauiy i
4-Cr 3 -2-pyndiny 1
-CH=N-N(CH 3 )-
2 =
j v-'F 2 z -pynainy i
o-Cr 3 -2-pyndinyl
-CH=N-N(CH 3 )-
2 =
T,u - ujivic-z.-pyriuiiiyi
A /"'T? 1 * * J * 1
4-Cr 2 -2-pynmidinyl
-CH 2 OC(SMe)=N-
2 -
3 • iiciiyi
3-Cr 3 -pnenyl
-CH20C(SMe)=N-
z =
*t-v^*—F j pneny i
J-UCr 3 -pnenyl
-CH20C(SMe)=N-
2 =
4-ci-pnenyl
-CH20C(SMe)=N-
2 =
j , uii^i -pneny i
3-Me-pnenyl
-CH20C(SMe)=N-
7 —
h— lvie-pnenyi
3,5-aiMe-phenyl
-CH20C(SMe)=N-
2 =
V_.fl annrnol Arvirl
z-napnuiaienyi
6-Me-2-pyridinyl
-CH 2 OC(SMe)=N-
2 =
t~ivic-^-^jy i luiiiy i
4,6-diMe-2-pyridinyl
-CH 2 OC(SMe)=N-
2 =
S— l*F^— 7— nvriHinvl
5-Mc-2 -pyndiny 1
-CH 2 OC(=S)NMe-
2 =
4— CFo-nVipnvl
-phenyl
-CH 2 OC(=S)NMe-
z -
4-OCF 3 -phenyl
j'VA/r ~z jjiiviiy 1
-CH 2 OC(=S)NMe-
z =
3-Cl-Dhenvl
*t-\^i -pneny 1
-CH 2 OC(=S)NMe-
Z =
3,5-diCl-phenyl
-CH 2 OC(=S)NMe-
z =
4-Me-Dhenvl
J j J uuvxc piiviiy 1
-CH 2 OC(=S)NMe-
z =
2-naphthalenyl
u ivic— ^— i lujij y 1
-CH 2 OC(=S)NMe-
Z =
4-Me-2-pyridinyl
4 ft— fiilV^"p— nvriHinul
"TjU-uiivic 4* ^yi liiuiyi
-CH 2 OC(=S)NMe-
Z =
5-CF 3 -2-pyridinyl
J 1V1C ^ LsjrilUlIiyi
-SCH 2 -
z =
2-Me-phenyl
£* j -J TJ 11 VI C — IJ 1 1 vll Jf J
-SCH 2 -
Z =
3-CF 3 -phenyl
4-CF 3 -phenyl
-SCH 7 -
z =
4-\4e-nhenv1
H-r-Du-pnenyi
-SCH->-
2 =
*t-L4-pnenyi
-SCH 2 -
Z =
2-Me-5-Cl-phenyl
* jj u uiicij y 1
-SCH 2 -
Z =
2-naphthalenyl
l-naphthalenyl
-SCH 2 -
Z =
3-pyridinyl
4-pyridinyl
-SCH 2 -
Z =
6-Me-2-pyridinyl
5,6,7,8-tetrahydro-2-
naphthalenyl
CH 2 0-N=C(SCH 3 >
Z =
3-CF 3 -phenyl
3-OCF 3 -phenyl
CH 2 0-N=C(SCH 3 >
Z =
3-Me-phenyl
4-CF 3 -phenyl
WO 99/28305
PCT/US98/24265
Y
-CH 2 0-N=C(SCH 3 )-
-CH 2 0-N=C(SCH 3 )-
-CH 2 0-N=C(cyclopropyl)-
-CH 2 0-N=C(cyclopropyl)-
-CH 2 0-N=C(cyclopropyl)-
-CH 2 0-N=C(cycIopropyl)-
R3 = CF 3
Y
-O-
-O-
-O-
-O-
-O-
-O-
-O-
-O-
-O-
-O-
-O-
-O-
-O-
-O-
-O-
-O-
-O-
-O-
-o-
-O-
-o-
-o-
-o-
-o-
-o-
94
("Vilnmn 1
i^oiumn z
z =
4-OCF 3 -phenyl
4-Me-phenyl
z =
3-Cl-phenyl
3,5-diCl-phenyl
2 =
3 -CF 3 -phenyl
3-OCF 3 -phenyl
z =
3-Me-phenyl
4-CF 3 -phenyl
Z =
4-OCF 3 -phenyl
4-Me-phenyl
Z =
3-Cl-phenyl
3,5-diCl-phenyl
Table 4c
Column 1
Column 2
Z-
Phenyl
3-OMe-phenyl
z =
4-CF 3 -phenyl
3-Me-phenyl
z =
3-F-phenyl
3-OCF 3 -phenyl
z =
4-Me-phenyl
3-I-phenyl
z =
3-SCH 3 -phenyl
2-Me-phenyl
z =
3-SCHF 2 -phenyl
4-SCH 3 -phenyl
z =
3-cyclohexyl-phenyl
4-SCHF 2 -phenyl
z =
6-CF 3 -2-pyridinyl
5-CF 3 -2-pyridiny 1
z =
4-CF 3 -2-pyridinyl
6-Me-2-pyridinyl
z =
0-(CF 3 CH 2 O)-4-pynmidinyl
5-Me-2-pyridinyl
z =
2-(CF 3 CH 2 0)-4-pyrimidinyl
4-(CF 3 CH 2 0)-2-pyrimidinyl
z =
4-Me-2-pyridinyl
3,5-diMe-phenyl
z =
2-naphthalenyl
5,6,7,8-tetrahydro-2-
naphthalenyl
z =
4-OCF 3 -phenyl
3-f-Bu-phenyl
z =
4-/-Bu-phenyl
6-(CF 3 CH 2 0)-2-pyrazinyl
z =
3-SCF 3 -phenyl
4-SCF 3 -phenyl
z =
4-CF 3 -6-Me-2-pyridinyl
3-CN-phenyl
z =
4, 6-diMe-2-pyridiny 1
3,5-di(CF 3 )-phenyl
z =
5-Cl-2-thiazolyl
5-I-2-thiazolyl
z =
5-OCF 3 -2-thiazolyl
5-(CH 3 ) 3 Si-2-thiazolyl
z =
5-CN-2-thiazolyl
5-SCH 3 -2-thiazolyl
z =
5-CF 3 -2-thiazolyl
4-Me-5-Cl-2-thiazolyl
z =
4-Me-5-I-2-thiazolyl
4-Me-5-CN-2-thiazolyl
z =
4-Me-5-CF 3 -2-thiazolyl
z =
3-(HCEC)-phenyl
3-(CH 3 C=C)-phenyI
WO 99/28305
PCT/US98/24265
95
Y
Column 1
Column 2
-O-
Z =
3-((CH 3 ) 3 CG=C)-phenyl
3-((CH 3 ) 3 SiCeC)-phenyl
-O-
Z =
3-( O^C==Q-phenyl
5-Me-2-thienyl
-o-
Z =
5-(CH3)3C-2-thienyl
-o-
Z =
5-Br-2-thienyl
5-1-2-thienvl
-o-
Z =
4-Me-2-thienyl
" v^* 1 3-'3 uiienyi
-o-
Z =
4-Cl-2-thienyl
■ 01 a uucuyi
-o-
Z =
4-I-2-thienyl
*t , j - uiivie-z-imeny 1
-o-
Z =
4-Me-5-Cl-2-thienyI
*+-ivie- j -jt>r-z- ttueny 1
-o-
Z =
4-Me-5-I-2-thienyl
i-z -roieny 1
-O-
Z =
5-Me-3-thienyl
3-^11.3^3 1^-0 -uuenyi
-o-
Z =
5-Cl-3-thienvI
j-bi- j - imeny 1
-o-
Z =
5-I-3-thienyl
*r-ivic- j - inicny 1
-o-
z -
4-(CH^)5 C-3-thienvl
4.f~'i.^.i-i L iif»m/i
*t~^i~j~miciiyi
-o-
Z =
4-Br-3-thienyl
/I T T tnianirl
H-i-j-LQicnyi
-o-
Z =
4,5-diMe-3-thienyl
H-ivic-j-i^io-xnicnyi
-o-
Z =
4-Me-5-Br-3-thienyl
*T-ivic-j-i-j-uiicnyi
-o-
z =
2-Cl-3-thienyl
-CH 2 0-
z =
Phenyl
-CH 2 0-
z =
2-Me-5-/-Pr-phenyl
7-\/fp_4 nrH« nhantil
-CH 2 0-
z =
4-OCF3-phenyl
-CH 2 0-
z =
3-OCHF 2 -phenyl
4-OPHF^-nhpnvl
-CH 2 0-
z =
3,5-di(CF3)-phenyl
-CH 2 0-
z =
6-CF3 -2-pyridinyl
^-DrP-> -r\hpr»\/l
j-\_/vj"2"puenyi
-CH 2 0-
z =
4-CF3 -2-pyridinyl
t-ivic - ^ ~py i luiny 1
-CH 2 0-
z =
2-Me-4-OCF 3 -phenyl
i— \^P— V— iwnninvl
j ivic A.*pyiiuiiijf 1
-CH 2 0-
z =
3,6-diMe-2-pyridinyl
-CH 2 0-
z =
4,6-diMe-2-pyridinyl
r\— I 11 mfnninifl
vr~V_y^i T - "Z.~|jy I ILlUIyl
-CH 2 0-
z =
4-CF 3 -6-Me-2-pyridinyl
>-\^p— 7— TYvriHinvl
j ivxfc a uy 1 luiiiy 1
-CH 2 0-
z =
4-Cl-2-pyrimidinyl
o-ivic-i-pynuxiiyi
-CH 2 0-
z =
4-CI-2-T>vrimiHinvl
-j-£.i-pnenyi
-CH 2 0-
z =
2,6-diMe-4-pyridinyl
2,4,6-triMe-phenyl
-CH 2 0-
z =
3-Cl-2-pyridinyl
6-Cl-4-pyrimidinyl
-CH 2 0-
z =
1-napthalenyl
2,3,6-triMe-phenyl
-CH 2 0-
z =
6-Cl-2-pyrazinyl
4-CF3-2-pyrimidinyl
-CH 2 0-
z =
6-CF3 -4-pyrimidinyl
2-/-Pr-phenyl
-CH 2 0-
z =
3-Me-2-pyridinyl
4-Cl-2-pyridinyl
WO 99/28305
PCT/US98/24265
96
Y
Column 1
column 2.
-OCH 2 -
Z =
2-Me-phenyl
2,5-diMe-phenyl
-OCH 2 -
Z =
3-CF 3 -phenyl
» vl "1 pilwljrl
-OCH 2 -
Z =
4-Me-phenyl
f-f-uu-pnenyi
-OCH 2 -
Z =
3-CI-phenyl
4-d-pnenyi
-OCHj-
Z =
3-/-Bu-phenyl
-OCH 2 -
Z =
2-naphthalenyl
1 -naphthalcny]
-OCH?-
z =
j jjyi luuiy i
4-pyridinyl
-OCH 2 -
z =
6-\te-2-"nvridinvl
z-(5, 6,7,8-
tetrahydro)naphthalenyl
-CH 2 0-N=C(CH 3 )-
Z =
3-\le-nhenv.
4-Cr 3 -phenyl
-CH 2 0-N=C(CH 3 )-
z =
3-Cl-phenyl
-CH 2 0-N=C(CH 3 )-
z =
4— Rr-nhpnvl
3,5-di(CF 3 )-phenyl
-CH 2 0-N=C(CHn)-
z =
4-f-Bu-phenyl
-CH 2 0-N=C(CH 3 )-
z =
^ - /- Rl 1 -nil An \A
5-CF 3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )-
z =
• ^vr^ piicny i
3-OCHF 2 -phenyl
-CH 2 0-N=C(CHo)-
z =
5-^^e-7 -nvri Hinvl
4-CF 3 -6-Me-2-pyndinyl
-CH 2 0-N=C(CH 3 )-
z =
4-Me-2-nvri fiinvl
4,6-diMe-2-pyridinyl
-CH 2 0-N=C(CH 3 )-
z =
f\— TVyl f*_ V _I\\7I"J /4 1 •%« rl
u ivic-z.-pyntiinyi
6-CF 3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )-
z =
6-OMc-2-pyridinyl
2 n— ni^^p— 4-nvrif1iTi\/1
-CH 2 0-N=C(CH 3 )-
z =
2 . 6-di CI -4-n vri H i n vl
D-UCr 3 -2-pyndinyl
-CH 2 0-N=C(CH 3 )-
z =
4-OM e-9 -nvriHi nvl
4-OCF 3 -2-pyndinyl
-CH 2 0-N=C(CH 3 )-
z =
5-OCHFi-2-nvriHinv1
o-uur 3 -2-pyndinyl
-CH 2 0-N=C(CH 3 )-
z =
4-OCHFo-nvrirfinvl
3-(Cr 3 LH 2 0)phenyl
-CH 2 0-N=C(CH 3 )-
z =
6-OCH K^-9-nvriHin\/1
v» *-»viii ^/ py i wxwxy 1
^-t,t-pnenyj
-CH 2 0-N=C(CH 3 )-
z =
1 -nanhtha Ipn vl
I ,z,3,4-tetrahydro-2-
naphthalenyl
-CH 2 0-N=C(CH 3 )-
z =
—» cjita v unciiy i
3-ethynylphenyl
-CH 2 0-N=C(CH 3 >
z =
f-Bu
0 T? ^ A^f^ — U«_, ,1
z-r-j-v^r 3-pnenyI
-CH=N-OCH(CH*)-
z =
4-PFi -nhpn vl
3-CF 3 -phenyl
-CH=N-OCH(CH?)-
z =
4-OCF-» -nhpnvl
~ v-/\^x' 3 -pijenyi
3-OCF 3 -phenyl
-CH=N-OCH(CH 3 )-
z =
3-Cl-phenyl
4-Cl-phenyl
-CH=N-OCH(CH 3 )-
z =
3,5-diCl-phenyl
3,5-di(CF 3 )-phenyl
-CH=N-OCH(CH 3 )-
z =
3-Me-phenyl
4-Me-phenyl
-CH=N-OCH(CH 3 )-
z =
2-naphthalenyl
4-OCHF 2 -phenyl
-CH=N-OCH(CH 3 >
z =
3-OCHF 2 -phenyl
4-CF 3 - 2-pyridinyl
-CH=N-OCH(CH 3 )-
z =
5-CF 3 -2-pyridinyl
6-CF 3 -2-pyridinyl
-CH=N-OCH(CH 3 )-
z =
4-Me-2-pyridinyl
5-Me-2-pyridinyl
WO 99/28305
PCT/US98/24265
97
Y
Column 1
Column
-CH=N-OCH(CH 3 )-
Z =
6-Me-2-pyridinyl
4— ( 1**^ — ft— AAA— *7_n\7f*i/^i¥i\/1
-CH=N-OCH(CH 3 )-
Z =
4-OCF 3 -2-pyridinyl
^>-w\_/r^-z-pynainyj
-CH=N-OCH(CH 3 )-
Z =
6-OCF 3 -2-pyridiny 1
4-OCHF-*-2-nvriHim/l
-CH=N-OCH(CH 3 )-
Z =
5-OCHF 2 -2-pyridinyl
o-v^^rir'2~-^"Pynainyi
-CH=N-OCH(CH 3 )-
Z =
3-r-Bu-phenyl
i-r\Vif»n\/l
-CH 2 -SC(Et)=N-
Z =
4-CF 3 -phenyl
j-^r 3 -pnciiyi
-CH 2 -SC(Et)=N-
Z =
4-OCF 3 -phenyl
j - vji— r a -pneny i
-CH 2 -SC(Et)=N-
Z =
3-Cl-phenyl
*+-^i-pnenyi
-CH 2 -SC(Et)=N-
Z =
3.5-diCl-nhenvl
j,j-ancr3j-pnenyl
-CH 2 -SC(Et)=N-
Z =
3-Me-phenyl
H-ivi e-pneny i
-CH 2 -SC(Et)=N-
Z =
3,5-diMe-phenyl
z-iiapjiuiaienyi
-CH 2 -SC(Et)=N-
Z =
6-Me-2-TYvridinvl
V 1TAV A* V*J * lUUlj 1
4-Me-2-pyridinyl
-CH 2 -SC(Et)=N-
Z =
4,6-diMe-2-pyridinyl
5-Cl-2-pyridinyl
-CH 2 -SC(Et)=N-
Z =
4 6-diCl-2-Dvridinv1
j-ivie-z-pynainyl
-CH 2 -SC(Et)=N-
z =
5-CF3 -2-pyridiny 1
j - DT- o- jvie-z-pynciinyl
-CH 2 -SC(=S)NMe-
z =
4-CFi -ohenvl
•s-v^r^-pnenyl
-CH 2 -SC(=S)NMe-
z =
4-OCF 3 -phenyl
-> vj\^.r 3 -pnenyi
-CH 2 -SC(=S)NMe-
z =
3-Cl-phenyl
t~v-/i"pjiciiyi
-CH 2 -SC(=S)NMe-
z =
3,5-diCl-phenyl
j,j"Ui^rij-pneiiyi
-CH 2 -SC(=S)NMe-
z =
3-Me-phenyl
4_FVi1 *»_»1ri anifl
< T~ivic~piienyi
-CH 2 -SC(=S)NMe-
z =
3,5-diMe-phenyl
V.nanntnalanifl
^.-iiapn uiaicny j
-CH 2 -SC(=S)NMe-
z =
6-Me-2-pyridinyl
^/l £»_ 0 _T\"\ 7t"t /^-i »*\^ tl
t-ivic- z.-py nuiny i
-CH 2 -SC(=S)NMe-
z =
4,6-diMe-2-pyridinyl
wi~ut"pyriouiyi
-CH 2 -SC(=S)NMe-
z =
4,6-diCl-2-pyridinyl
j -ivic-^.-py nuiny 1
-CH 2 -SC(=S)NMe-
z =
5-CF 3 -2-pyridiny 1
j di ~u *vic-i-pynoiiiyi
-CH 2 SC(SMe)=N-
z =
3-Me-phenyl
-CH 2 SC(SMe)=N-
z =
3,5-diMe-phenyl
j wi-piiciiyi
-CH 2 SC(SMe)=N-
z =
4-Cl-phenyl
j>-/ uiwi-pncnyi
-CH 2 SC(SMe)=N-
z =
3-CF 3 -phenyl
A_i ' Ih'm i\kamrl
*t-^r 3-pnenyi
-CH 2 SC(SMe)=N-
z =
3-OCF 3 ~phenyl
*T-L^l_/r ^-pnenyi
-CH 2 SC(SMe)=N-
z =
3,5-di(CF 3 )-phenyl
-CH 2 SC(SMe)=N-
z =
t-Bu
2-naphthalenyl
-CH 2 SC(SMe)=N-
z =
6-Mc-2-pyridinyl
4-Me-2-pyridinyl
-CH 2 SC(SMe)=N-
z =
4,6-diMe-2-pyridinyl
5-Cl-2-pyridinyl
-CH 2 SC(SMe)=N-
z =
4,6-diCl-2-pyridinyl
5-Me-2-pyridinyl
-CH 2 SC(SMe)=N-
z =
5-CF 3 -2-pyridinyl
5-Br-6-Me-2-pyridinyl
-CH 2 S-
z =
2-Me-phenyl
3-CF 3 -phenyl
WO 99/28305
PCTAJS98/24265
98
Y
Column 1
-CH 2 S-
Z =
4-CFi-Dhenvl
2,5-diMe-phenyl
-CH 2 S-
z =
2-Et-phenyl
"^-Pl-nhprn/l
J~ wl-JJUVlljf I
-CH 2 S-
z =
2-Cl-phenyl
z, j-aiL^i-pnenyi
-CH 2 S-
z =
4,6-diMe-2-pyrimidinyl
4-A/ff»-1 9 4_t~Hci7rk1 'l i ;l
t-ivic- 1 ,z,H-iriazoi- j-yi
-CH 2 S-
z =
2-naphthalenyl
i -ivie-z-iiniaazoiyi
-CH 2 S-
z =
4— \/tp-^-r>vriTTiiH inx/1
j-ivie- i t jj^-tniaaiazol-z-yl
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
3-Me-nhenvl
2 -Me-phenyl
-CH 2 0-N=C(CH 3 )CH 2 S-
z -
-* >»»x ^ tvixcxiyx
4-Cr3-pnenyl
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
3-Cl-nhenvl
z-ct-pnenyi
-CH 2 0-N=C(CH 3 )CH->S-
z =
4- C 1 ! -n h *»nvl
z-napntnalenyl
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
4-(_r 3 -z-pyndinyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
^-IVfs-Tihenvl
2-Me-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4 -ft/4 P-r» Vl pnvl
■ xvxv* pxlGxljrl
3-L,r3-pnenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4-CF-5-nhenv1
4-L-J-pnenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
3-Cl-phenyl
3 , 5 -diMe-pheny 1
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
2 . 5-diMe-nhenvl
z -jvie-j- i -jr r-pneny l
-CH 2 0-N=C(CH 3 )CH 2 0-
7. =
3-Et-phenyl
v-v^r^-z-pyncjinyi
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4-CF 3 -2-pyridinyl
^ v^r^-z -py 11 ainyi
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
6-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4-Me-2-pyridinyl
1 XtoLfllLLlCllCliy 1
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
2-naphthalenyl
z-v_.F o -pnenyi
-CH 2 CH 2 -
z =
2-Me-phenyl
z, j-uiivie-piienyi
-CH 2 CH 2 -
z =
3-CF 3 -phenyl
^ 'i "i -piiciiyi
-CH 2 CH 2 -
z =
3-Cl-phenyl
i vi ^/xiciiyi
-CH 2 CH 2 -
z =
3-OCF 3 -phenyl
4-OPF-i -nhpnvl
-CH 2 CH 2 -
z =
2-Et-phenyl
^ ivic~j"^i-piiciiyi
-CH 2 CH 2 -
z =
2-naphthalenyl
j,u-uiiVie-z-pyriuiiiyi
-CH=C(CH 3 )-
z =
3-Me-Dhenvl
*T-jvie-pnenyi
-CH=C(CH 3 )-
z =
3,5-diMe-phenyl
j-wi-pnenyi
-CH=C(CH 3 )-
z =
4-Cl-phenyl
j-^\^r 3 -pnenyi
-CH=C(CH 3 )-
z =
4-OCF 3 -phenyl
3-CF 3 -phenyl
-CH=C(CH 3 )-
z =
4-CF 3 -phenyl
2-naphthalenyl
-CH=C(CH 3 )-
z =
4-CF 3 -2-pyridiny 1
6-CF 3 -2-pyridinyl
-CH=N-N=C(CH 3 )-
z =
3-Me-phenyl
4-Me-phenyl
-CH=N-N=C(CH 3 )-
z =
3 -CF 3 -phenyl
4-CF 3 -phenyl
-CH=N-N=C(CH 3 )-
z =
3-OCF 3 -phenyl
4-OCF 3 -phenyl
-CH=N-N=C(CH 3 )-
z =
3,5-diMe-phenyl
3-Cl-phenyl
WO 99/28305
PCT/US98/24265
99
Y
Column 1
\-r\Jl\llkUX Z
-CH=N-N=C(CH,)-
Z =
4-Cl-phenyl
J, j-un^i-pnciiy 1
-CH=N-N=C(CH 3 )-
Z =
4-CF-2 -2-Dvridinvl
j-v-r 3-z-pyriainyi
-CH=N-N=C(CH 3 )-
z-
6-CFq -2-nvridinvl
t-ivie - z-py nuinyi
-CH=N-N=C(CH 3 )-
z =
5 -Me-2 -pyridinyl
u"ivic"x*pj'nuiiiyi
-CH=N-N=C(CH 3 )-
z =
2-naphthalenyl
** , o-uiivic-z -p ynomy 1
-CH=N-N=C(CH 3 )-
z =
3-E t-nh en vl
/ Tin
i-DU
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
3 -Me-nhen vl
4-Me-phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH?)-
z =
.j-d-pnenyl
-CH 2 0-N=C(CH 3 )C(=NOCHo)-
z =
4-Cl-nhenvl
0 ,j -aid-pnenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z -
3 - CF3 -phenyl
H-v^r 3-pnenyi
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
3 5-fhYCF-aVnhenvl
3-pnenyi
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-OCF3-phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
*-Bu
2-naphtha leny 1
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z
4-i*-Bu-nhenv1
4-Me-2 -pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z-
5-Me-2-nvridinvl
6-Me-2 -pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-CF 3 -2-pyridinyl
j \~>r 3 *z-py nuiny i
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
6-CF 3 -2-pyridinyl
•t , u~uiivxc ~z-py nuiDy j
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-CFi-2-Dvrimidinvl
o-v-r 3 -z-pyniniciiny 1
-CH=N-N(CH 3 )-
z =
3-Me-phenyl
4-> _ T\ nt^nvl
™ i"-ic~pucuy 1
-CH=N-N(CH 3 )-
z =
3,5-diMe-phenyl
3-Cl-nhenvl
-CH=N-N(CH 3 )-
z =
4-CI-phenyl
3 5-diPI-nhenvl
-CH=N-N(CH 3 >
z =
3-CF 3 -phenyl
1 \w- x 1 yucuyi
-CH=N-N(CH 3 >
z =
3-OCF 3 -phenyl
4-OPF^-nhpnvl
-CH=N-N(CH 3 )-
z =
2-naphthalenyl
4-/-"Rii-fiViPTivl
■t i*jju~ Liiiciiy 1
-CH=N-N(CH 3 )-
z =
4-Me-2 -pyridinyl
j — ivi c "*z py 1 lutiiyi
-CH=N-N(CH 3 >
z =
6-Me-2-pyridinyl
t-v^i i -z-pyi iciniy 1
-CH=N-N(CH 3 )-
z =
5-CFi-2-t)vridinvl
^-z-pyxiuuiyi
-CH=N-N(CH 3 )-
z =
4.6-diMe-2-nvridinv1
*T"v^jTj-z-pyriiiiiainyi
-CH 2 OC(SMe)=N-
z =
4-CF 3 -phenyl
-CH 2 OC(SMe)=N-
z =
4-OCFi-ohenvl
j-uv/f 3 -pneny 1
-CH 2 OC(SMe)=N-
z =
3-Cl-phenyl
4-Cl-phenyl
-CH 2 OC(SMe)=N-
z =
3,5-diCl-phenyl
3-Me-phenyl
-CH 2 OC(SMe)=N-
z =
4-Me-phenyl
3,5-diMe-phenyl
-CH 2 OC(SMe)=N-
z =
2-naphthalenyl
6-Me-2-pyridinyl
-CH 2 OC(SMe)=N-
z =
4-Me-2-pyridinyl
4,6-diMe-2-pyridinyl
-CH 2 OC(SMe)=N-
z =
5 -CF 3 -2-pyridiny 1
5-Me-2-pyridinyl
-CH 2 OC(=S)NMe-
z =
4-CF 3 -phenyl
3-CF3-phenyl
WO 99/28305
PCT/US98/24265
100
Y
Column 1
L,oxumn 2.
-CH 2 OC(=S)NMe-
Z =
4-OCF3 -phenyl
^-w^r^-pnenyi
-CH 2 OC(=S)NMe-
Z =
3-Cl-phenyl
/I /""M fJ
*t"V^i-pncnyi
-CH 2 OC(=S)NMe-
Z =
3,5-diCl-phenyl
j -lvie -pncnyi
-CH 2 OC(=S)NMe-
Z =
4-Me-phenyl
3,5-dilVle-plienyl
-CH 2 OC(=S)NMe-
z =
2-nanhthalenvl
6-Me-2 -pyridiny 1
-CH 2 OC(=S)NMe-
Z =
4-Me-2-nvridinvl
H-,o-aiJVLe-z-pynuinyi
-CH 2 OC(=S)NMe-
z =
-2-nvridinvl
5 -Me-2-pyridinyl
-SCH 2 -
z =
2-Me-Dhenvl
2,5-diMe-phenyl
-SCH 2 -
z =
3-CF3~phenyl
4-CFt -nhpnvl
-SCH ? -
z =
4-Me-nhenvl
q -/-ou-pneny I
-SCH 2 -
z =
3-Cl-nhenvl
4-ci-pnenyl
-SCH7-
z =
^ lvic- j - v- i-uiieiiy 1
3-/-Bu-phenyl
-SCH 2 -
z =
xilaJJilU lalcllV J
1-naphthalenyl
-SCH 2 -
z =
4-pyridinyl
-SCH 2 -
z =
5,o,7,8-tetrahydro-2-
naphthalenyl
-CH->0-N=CfSCH^V
z =
-> v^r^ pnenyi
3-OCF 3 -phenyl
-CH 2 0-N=C(SCHh)-
z =
4-CF 3 -phenyl
-CH 2 0-N=C(SCH 3 )-
z =
4-OCF 3 -phenyl
4-Me-phenyl
-CH 2 0-N=C(SCH 3 )-
z —
»>~\--i-pnenyi
3,5-diCl-phenyl
-CH 2 0-N=C(cyclopropyl)-
z =
3-CFo -nhenvl
j-wL-r 3 -pnenyi
-CH 2 0-N=C(cyclopiopyl)-
z =
3-Me-phenyl
^ -\_>.r 3 pncnyi
-CH 2 0-N=C(cyclopropy]>
z =
4-OCF 3 -phenyl
4-Me-phenyl
-CH 2 0-N=C(cyclopropyl>
z =
3-Cl-phenyl
3 , 5-diCl-pheny I
Table 5a
= CH 3
Y
Column 1
fnhimn 7
-O-
z =
Phenyl
^ I 1 ( ' n li i> fi \ r 1
J W1VAC— ^jiiciiy 1
-O-
z =
4-CF 3 -phenyl
3-Me-phenyl
-O-
z =
3-F-phenyl
3-OCF 3 -phenyl
-O-
z =
4-Me-phenyl
3-I-phenyl
-O-
z =
3-SCH 3 -phenyl
2-Me-phenyl
-O-
z =
3-SCHF 2 -phenyl
4-SCH 3 -phenyl
-O-
z =
3-cyclohexyl-phenyl
4-SCHF 2 -phenyl
-O-
z =
6-CF 3 -2-pyridinyl
5-CF 3 -2-pyridinyl
WO 99/28305
PCT/US98/24265
101
Y
• Column 1
-O-
z =
4-CF-a-2-Dvridinvl
6-Me-2-pyridinyl
-0-
z =
6-(CF3CH20)-4-pyrimidinyl
S-rt4f»-V-n\/riHin\/1
-0-
z =
2-(CF-j CH->0)-4-pvrimidinvl
^-v^^^r^^-z-pynmidinyl
-o-
z =
4-Me -2 -d vri d i n vl
3,5-duMe-phenyl
-o-
z =
2-naphthalenyl
j»d, / , 0 ic uany oro~z -
iiapnuiaienyi
-o-
z =
4-OCF3-phenyl
j * - jj u-piicnyi
-o-
z =
4-f-Bu-phenyl
u-^r3v w ,ri2^-z-pyrazuiyl
-o-
z =
3 -SCF3 -phenyl
**-ocr 3 -pnenyl
-o-
z =
4-CF'5-6-Me-2-nvriHinv1
^-l, in -pnenyl
-o-
z =
4 6-diN4e-9-nvriHin\/l
* ? utiviv ^ uyi ivjuiy 1
J ,5 -di(CF3)-phenyl
-o-
z =
5-Cl-2-thiazolyl
j-i-z-miazoiyi
-o-
z =
5-OCFi-2-thiazolvl
• 3 -\.^ri3;3oi-2-tnja20iyl
-o-
z =
5-CN-2-thiazolyl
j ~»>v^ri3 -uiidzoiyi
-o-
z =
5-CF 3 -2-thiazolyl
4-Me-5-Cl-2-thiazolyl
-o-
z =
4-Me-5-I-2-thiazolyl
4-Me-5-CN-2-thiazolyl
-o-
z =
4-Me-5-CF 3 -2-thiazolyl
-o-
z =
3-(HC£C)-phenyl
3-(CH 3 C=C)-phenyl
J f ST *
-o-
z =
3-((CH 3 ) 3 CC=C)-phenyl
3-((CH 3 ) 3 SiOCVphenyl
-o-
z =
3-( P>-C=Q-phenyl
5-Me-2-thienyI
-o-
z =
5-(CHa)o C-2-thienvl
i-z-imcnyi
-o-
z =
5-Br-2-thienyl
-0-
z =
4-Me-2-thienyl
t-^^n.3 ^3 ^"•^"inienyj
-o-
z =
4-Cl-2-thienyl
4- Fl r- 9 -th i on\/l
*t-iji -x-uiienyi
-o-
z =
4-I-2-thienyl
*t , j - uuvic- xnieny i
-o-
z =
4-Me-5-Cl-2-thienyl
4-M>-^-Rr_9_thip»«\/1
"t ivxc-j-Di-^-imciiyi
-o-
z =
4-Me-5-I-2-thienyl
^ fl 9 thianvrl
j v^i Z'Uiicnyi
-0-
z =
5 -Me-3-thienvI
j-t^i-13 ^3 L.-3-tnienyI
-o-
z =
5-Cl-3-thienvl
-> -or-3-tnienyl
-o-
z =
5-I-3-thienyl
4-Me-3-thienyl
-o-
z =
4-(CH 3 ) 3 C-3-thienyl
4-Cl-3-thienyl
-o-
z =
4-Br-3-thienyl
4-1-3 -thienyl
-0-
z =
4,5-diMe-3-thienyl
4-Me-5-Cl-3-thienyl
-o-
z =
4-Me-5-Br-3-thienyI
4-Me-5-I-3-thienyl
-o-
z =
2-Cl-3-thienyl
2-CF3 -phenyl
CH 2 Q-
z-
Phenyl
3-CF3-phenyI
WO 99/28305
PCT/US98/24265
102
Y
Column 1
Column 9
-CH 2 0-
Z =
2-Me-5-/-Pr-phenyl
2-Me-4-OPH-> -nhenvl
-CH 2 0-
Z =
4-OCF 3 -phenyl
2-Me-5-CFT -nhenvl
-CH 2 0-
Z =
3-OCHF?-phenyl
4-OPfTF *\ -nVipnvl
-CH 2 0-
Z =
3,5-di(CF*)-phenyl
-CH 2 0-
Z =
6-CF-i -2-Dvridinvl
-CH 2 0-
Z =
4-CF 3 -2-pyridinyl
*r - jvie -z-py numy i
-CH 2 0-
Z =
2-Me-4-OCF 3 -phenyl
5 -Me-2-pyndiny 1
-CH 2 0-
Z =
3,6-diMe-2-pyridinyl
j ^r^-z-pyriaiiiyi
-CH 2 0-
Z =
4,6-diMe-2-Dvridlnvl
o-u^r 3 -z-pynainyl
-CH 2 0-
Z =
4-CF 3 -6-Me-2 -pyridinyl
> — 1^1 P — / — M vn H i ri v 1
-* xviv Xr pjrllullljrl
-CH 2 0-
Z =
4-Gl-2-DViimidinvl
6-Me-2 -pyridinyl
-CH 2 0-
Z =
4-Cl-2-Dvrimidinvl
■ ■^-•"i ft j * uiiiumy a
3-Et-phenyl
-CH 2 0-
Z =
2, 6~diMe-4 -pyridinyl
2,4,6-t^i^4e-phenyI
-CH 2 0-
Z =
3-Cl-2-pyridinyl
6 -CI -4-pyrimidiny 1
-CH 2 0-
z =
1 -nanthalenvl
A3,o-triMe-pnenyl
-CH 2 0-
z =
6-Cl-2-Dvra7invl
4-CF3 -2-pyrimidiiiyl
-CH 2 0-
z =
6"CF'j-4~OVTtmidinvl
2-i-Pr-phenyl
-CH 2 0-
z =
3-Me-2 -pyridinyl
&JC*\-0 -tx\JT\f\xr\\T\
-OCH 2 -
z =
2-Me-phenyl
*"i<j uiivicpuciiyi
-OCH 2 -
z =
3 -CF 3 -phenyl
4-CF3 -phenyl
-OCH 2 -
z =
4-Me-phenyl
4— /-R 1 1 -n l"if»T«/l
■ * .ou-piiciiyi
-OCH 2 -
z =
3-Cl-phenyl
t-wi-pnenyi
-OCH 2 -
z =
2-Me-5-Cl-nhenvl
3-/-Bu-phenyl
-OCH 2 -
z =
2-naphthalenyl
1 — nsiTiritrmlATi^/l
1 iiopiiliialciiyi
-OCH 2 -
z =
3-pyridinyl
H-pynainyi
-OCH 2 -
z =
6-Me-2-pyridinyl
6 7 8-
V^jO, / t o-
icuanyuru jnapninaicny 1
-CH 2 0-N=C(CH 3 )-
z =
3-Me-phenyl
-CH 2 0-N=C(CH 3 )-
z =
3.5-diMe-nhpnvl
j-ci-pnenyi
-CH 2 0-N=C(CH 3 )-
z =
4-Br-phenyl
3,o-ai(Cr3)-pnenyl
-CH 2 0-N=C(CH 3 )-
z =
4-OCHF 2 -phenyl
4-NBu-phenyl
-CH 2 0-N=C(CH 3 )-
z =
3-f-Bu-phenyl
5-CF 3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )-
z =
4-OCF 3 -phenyl
3-OCHF 2 -phenyl
-CH 2 0-N=C(CH 3 )-
z =
5-Me-2-pyridinyl
4-CF 3 -6-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )-
z =
4-Me-2-pyridinyl
4,6-diMe-2-pyridiny3
-CH 2 0-N=C(CH 3 )-
z =
6-Me-2-pyridinyl
6-CF 3 -2-pyridiny 1
-CH 2 0-N=C(CH 3 )-
z =
6-OMe-2-pyridinyl
2,6-diMe-4-pyridinyl
WO 99/28305
PCT/US98/24265
103
Y
Column 1
Column 2
-CH 2 0-N=C(CH 3 >
Z =
2,6-diCl-4-pyridinyl
5-OCF 3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )-
Z =
4-OMe-2-pyridinyl
4-OCF 3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )-
Z =
5-OCHF 2 -2-pyridinyl
6-OCF 3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )-
Z =
4-OCHFi-Dvridinvl
3-(CF 3 CH 2 0)phenyl
-CH 2 0-N=C(CH 3 >
Z =
6-OCHF^-2-nvrtfiinvl
3-Et-phenyl
-CH 2 0-N=C(CH 3 )-
z =
1 -nanTith»1f»n\/1
i iia^suuiaiciiyi
l,2,3,4-tetrahydro-2-
naphthalenyl
-CH 2 0-N=C(CH,)-
z =
-/"Oivic-piioiiyi
3-ethynylphenyl
-CH 2 0-N=C(CH 3 )-
Z =
f-Bu
2-F-5-CF 3 -phenyl
-CH=N-OCH(CH*V
Z =
4-CFo -nhenvl
3-CF 3 -phenyl
-CH=N-OCH(CH 3 )-
z =
3-OCF 3 -phenyl
-CH=N-OCH(CH 3 )-
z =
3-C1 -nhenvl
4-Cl-phenyl
-CH=N-OCH(CH,)-
v J'
z =
3 5-diCl-Dhenvl
3,5-di(CF 3 )-phenyl
-CH=N-OCH(CH 3 )-
z =
3 -Me -phenyl
4-Me-phenyl
-CH=N-OCH(CH 3 )-
z =
2-naphthalenyl
4-OCHF 2 -phenyl
-CH=N-OCH(CH-0-
z =
3-OCHF^-nhenvl
4-CF 3 -2-pyridinyl
-CH=N-OCH(CH,)-
z =
j — i F *> — / ^iwri H i ti a/1
-» v^r^ -pyxiumyi
6-CF 3 -2-pyridinyl
-CH=N-OCH(CH 3 )-
z =
* ataw l/ y iiuiiiy i
5-Me-2-pyridinyl
-CH=N-OCH(CH 3 )-
z =
6-Me-2 -pyri dinyl
4-CF 3 -6-Me-2-pyridinyl
-CH=N-OCH(CH,)-
z =
4-OCFo-2-nvridinvl
5-OCF 3 -2-pyridinyl
-CH=N-OCH(CH 3 )-
z =
6-OCF-a -2-ovridi nvl
4-OCHF 2 -2-pyridinyl
-CH=N-OCH(CH,)-
z =
5-OCHF->-2-nvririinvl
6-OCHF 2 -2-pyridinyl
-CH=N-OCH(CH 3 )-
z =
3-/-Bu-phenyl
4-f-Bu-phenyl
-CH 2 -SC(Et)=N-
z =
4-CF^-Dhenvl
3-CF 3 -phenyl
-CH 2 -SC(Et)=N-
z =
4-OCF?-Dhenvl
3-OCF 3 -phenyl
-CH 2 -SC(Et)=N-
z =
3 -O-pheny 1
4-Cl-phenyl
-CH 2 -SC(Et)=N-
z =
3 5-diCl-nhenvl
3,5-di(CF 3 )-phenyl
-CH 2 -SC(Et)=N-
z =
3 -Me-phenyl
4-Me-phenyl
-CH 2 -SC(Et)=N-
z =
3,5-diMe-phenyl
2-naphthalenyl
-CH 2 -SC(Et)=N-
z =
\j avis— x-JJ^rllulilyl
4-Me-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
4,6-diMe-2-pyridinyl
5-Cl-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
4,6-diCl-2-pyridinyl
5-Me-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
5-CF 3 -2-pyridinyl
5-Br-6-Me-2-pyridinyl
-CH 2 -SC(=S)NMe-
z =
4-CF 3 -phenyl
3-CF 3 -phenyl
-CH 2 -SC(=S)NMe-
z =
4-OCF 3 -phenyl
3-OCF 3 -phenyl
-CH 2 -SC(=S)NMe-
z =
3-Cl-phenyl
4-Cl-phenyl
-CH 2 -SC(=S)NMe-
z =
3,5-diCl-phenyl
3,5-di(CF 3 )-phenyl
WO 99/28305
PCT/US98/24265
104
Y
AM lt^ln 1
Column 2
-CHo-SCf=S)NMe-
7 —
z. —
3 -Me-phenyl
4-Me-phenyl
-CH 2 -SC(=S)NMe-
7 —
3 ,5-diMe-pheny 1
2-naphthalenyl
-CH 2 -SC(=S)NMe-
7 —
6-Me -2 -py ridiny 1
4-Me-2-pyridinyl
-CH 2 -SC(=S)NMe-
2 =
4 , 6-diM e-2-pyndinyl
5-Cl-2-pyridinyl
-CH 2 -SC(=S)NMe-
2 =
H,o-uid-z-pyriciinyl
5-Me-2-pyridinyl
-CH 2 -SC(=S)NMe-
7 —
j -cr 3 -ii-pynainyl
5-Br-6-Me-2-pyridinyl
-CH 2 SC(SMe)=N-
7 —
z* —
3 -Me-phenyl
4-Me-phenyl
-CHoSCfSMel=N-
7 —
Zi —
3,5-diMe-phenyI
3-Cl-phenyl
-CH-i SCfSMe^N-
7 —
Z. —
4-Ci-pnenyl
3,5-diCl-phenyl
-CH 2 SC(SMe)=N-
7 —
Z, —
3 -phenyl
4-CF3 -phenyl
-CH 2 SC(SMe)=N-
7 —
j -vJCr 3 -pnenyI
4-OCF 3 -phenyl
-CH 2 SC(SMe)=N-
z =
->»-5~cii^r 3 j-pnenyi
CH 2 CH 2 -/-Bu
-CH 2 SC(SMe)=N-
2 =
*-x>u
2-naphthalenyl
-CH 2 SC(SMe)=N-
2 =
6-Me-2-pyridinyl
4-Me-2-pyridinyl
-CH 2 SC(SMe)=N-
2 =
n, o-uiivie-z-pyndinyl
5-Cl-2-pyridinyl
-CH 2 SC(SMe)=N-
2 =
o-ai^i-z-pynuinyi
5-Me-2-pyridinyl
-CH 2 SC(SMe)=N-
2 =
^ v^r 3 -z-pyriuinyi
5-Br-6-Me-2-pyndinyl
-CH 2 S-
7 —
Z, —
2-Me-phenyl
3-CF3-phenyl
-CH 2 S-
7 —
A /~" 1 T .1
4-Cr3-pnenyl
2,5-diMe-phenyl
-CH 2 S-
7 —
2-Et-phenyl
3-Cl-phenyl
-CH 2 S-
Z, —
2-Ci-pnenyl
2,5-diCl-phenyl
-CH 2 S-
7 —
Zj —
4,6-diMe-2-pyrimidinyl
4-Me- 1 ,2,4-triazol-3-yl
-CH-)S-
7 =
Z* * —
2-naphthalenyl
l-Me-2-imidazolyl
-CH 2 S-
7 —
4-Me-2-pyrimidinyl
5-Me- l,3,4-thiadiazol-2-yl
-CHoO-N=Cf CH^'iCHo S-
7 —
Zj —
3-Me-phenyl
2-Me-phenyl
-CH70-N=C(CH^)CH-»S-
7 =
Zw —
j-^r 3-pnenyl
4-CF 3 -phenyl
-CH->0-N=C(CHhK:H-iS-
7 _
Z, —
j-d-pnenyl
2-Et-phenyl
-CHoO-N^fCH^ICHiS-
7 —
Z- —
4-i_l-pnenyl
2-naphthalenyl
-CH?0-N=C(CHi}CHiS-
7 —
Z, —
z.s-aiMe-pnenyl
4-CF 3 -2-pyridinyl
-CHoO-N=C(CH-j}CH->0-
7 —
Zw —
3-Me-phenyl
2-Me-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4-Me-phenyl
-CH 2 0-N=C(CH3)CH 2 0-
z =
4-CF3-phenyl
4-Cl-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
3-Cl-phenyl
3,5-diMe-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
2,5-diMe-phenyl
2-Me-5-/'-Pr-phenyl
-CH 2 0-N=C(CH 3 )CH 2 O-
z =
3-Et-phenyl
6-CF3-2-pyridinyl
-CH 2 0-N=C(CH 3 )CH 2 O-
z =
4-CF3 -2-pyridinyl
5-CF3-2-pyridinyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
6-Me-2-pyridinyl
5-Me-2-pyridinyl
WO 99/28305
PCT/US98/24265
105
Y
vUIUillll i
voiumn z
-CHt 0-N=Cf CHi 1CH-»0-
£-1 —
4 -Me-2 -pyndiny 1
1-naphthalenyl
-CH')0-N=CfCHi»"iCH- > 0-
7 =
2-naphthalenyl
2-CF3-phenyl
V^l llvi 2-
7 —
2-Me-phenyl
2,5-diMe-phenyl
-CH->CH->-
7 —
3 -CF 3 -phenyl
4-CF3 -phenyl
-CH2CH2-
Z =
o~vi-pncnyi
4-Cl-phenyl
-CHiCH->-
7 —
j - v* v r 3 -pnenyi
4-OCF3-phenyl
-CH->CH->-
7 —
2 -Et-pheny 1
2-Me-5-Cl-phenyl
-CH->CH->-
v»>i I fV/i 1'7
7 —
£_. —
2-naphthalenyl
3,6-diMe-2-pyridinyl
-PH=PfPH^
Z. —
3-Me-phenyl
4-Me-phenyl
-CH=CCCH-> 1-
7 —
Z. —
3,5-diMe-phenyl
3-Cl-phenyl
Vll VI V117 i"
7 _
Z, —
4- CI -phenyl
3-OCF3-phenyl
^n~* v^ vn^ )~
Z. —
4-OCF3 -phenyl
3-CF3-phenyl
Z —
4-vr 3 -phenyl
2-naphthalenyl
7 —
Z- —
4- tr 3 -z-pynainyl
6-CF3-2-pyridinyl
-CH=N-N=P('PFU ^
vii 11 11 "vyvni^-
Z —
3-Me-phenyl
4-Me-phenyl
vii 11 11 v^vll^j*
7 —
Z —
j-vr3-ptienyl
4-CF3 -phenyl
-PH=N-N=PfPT-U ^
vl 1 11 11 v^ vil'3 ^~
Z. —
i-UCf^-pnenyl
4-OCF3-phenyl
-PH=N-?\I=P/'PW~. ^
z —
3,5-aiMe-phenyl
3-Cl-phenyl
Vll 1 1 "11""^Vlll j
Z. —
4-vi-pnenyl
3,5-diCl-phenyl
-CH=N-N=Pl'PTf -* ^
vll 11— li — v^vX17 )~
Z, —
4-vr3-2-pynainyl
5-CF3-2-pyridinyl
-CH=N-N=P^PH->\-
vii 11 11 v^vXl'i/
7 —
Zy —
o-Lr 3-2-pynainyl
4-Me-2-pyridinyl
-CH=N-N=C^CH-> V
Vl 1 11 11 V^V^l 17 1—
7 —
z, —
5-Me-2-pyridinyl
6-Me-2-pyridinyl
-CH=N-N=CfCH? V
* A ' * ~ vi vii ~S /
7 —
z-napuinaienyi
4,6-diMe-2-pyndinyl
-CH=N-N=CCCHo V
N -^- H - A * 1 11 V — (Vll A /
7 —
3-Et-phenyl
r-Bu
-CHoO-N^fCH^C^NOCHoV
7 =
3-Me-phenyl
4-Me-phenyl
viA^v 11 v^Vllj^v^ 11 v* v A 1"2 y
3,5-diMe-phenyl
3-Cl-phenyl
Vll^ V 1 1 v^ VI 1 i^V^ 1 1 WvJIl h~
7 —
Z- —
*fr-vi-piienyi
3,5-diCl-phenyl
-CHoO-N=CfCHa}Cf=NOCH->V
7 —
j-vr 3 -pnenyi
4-CF3 -phenyl
-CHiO-N=CY CH-j W=Nnr"Hi \
vn^v 11 v\ vi ijyv^ liUvnij-
7 —
Z —
3,->-ai^Cr 3 )-pnenyl
3-OCF3-phenyl
-CHiO-N=cccHi , irr=NorH^ , >
vii^v 11 V'^viiiyV'^ i"( WvilT 1
7 —
Z. —
/I /^\/— 'C 1 |
4-u vr 3 -phenyl
CH3
-CH 2 0-N=C(CH3)C(=NOCH 3 )-
Z =
/-Bu
2-naphthalenyl
-CH 2 O.N=C(CH 3 )C(=NOCH3)-
Z =
4-/-Bu-phenyl
4-Me-2-pyridinyl
-CH 2 0-N=C(CH3)C(=NOCH 3 )-
z =
5-Me-2-pyridinyl
6-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-CF3-2-pyridinyl
5-CF3-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
6-CF3-2-pyridinyl
4,6-diMe-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-CF3-2-pyrimidinyl
6-CF3-2-pyrimidinyl
-CH=N-N(CH 3 >
z =
3-Me-phenyl
4-Me-phenyl
WO 99/28305
PCT/US98/24265
106
Y
Column 1
^ column 1
-CH=N-N(CH 3 )-
Z =
3,5-diMe-phenyI
j-d-pnenyi
-CH=N-N(CH 3 )-
Z =
4-C1 -phenyl
j,j-aid-pnenyi
-CH=N-N(CH 3 )-
Z =
3-CFa -ohenvl
H-v^r^-pnenyi
-CH=N-N(CH 3 )-
z =
j-OCF^ -nhpnvl
^t-ucr 3 -pnenyl
-CH=N-N(CH 3 )-
Z =
2-naphthaleny 2
^-i-t>u-pnenyl
-CH=N-N(CHo)-
Z -
*t-ivic --i-py nainy i
5-Me-2-pyridinyl
-CH=N-N(CHi)-
z =
u-ivic - -&"py nuinyi
4-CF 3 -2-pyridinyl
-CH=N-N(CH 3 )-
z =
5-CF^-2-pyndiiiyI
6-CF 3 -2-pyridinyl
-CH=N-N(CH 3 )-
z =
*t s u-uuvie -z-pynamy i
4-CF 3 -2-pyrimidinyl
-CH 2 OC(SMe)=N-
z =
t-^-r 3-pnenyj
3-CF 3 -phenyl
-CH 2 OC(SMe)=N-
z =
" uv^r^ -pnenyj
3-OCF 3 -phenyl
-CH 2 OC(SMe)=N-
z =
4-Cl-phenyl
-CH 2 OC(SMe)=N-
z =
LLIV^l*L>IiCIly I
3-Me-phenyl
-CH 2 OC(SMe)=N-
z -
*t- jvie -pneny 1
3,5-diMe-phenyl
-CH 2 OC(SMe)=N-
z =
x-udpnuiaienyj
6-Me-2-pyridinyl
-CH 2 OC(SMe)=N-
z =
t-ivxe -z-pynuiny 1
4,6-diMe-2-pyndinyl
-CH 2 OC(SMe)=N-
z =
*/ t"pynuiiiyi
5-Me-2-pyridinyl
-CH 2 OC(=S)NMe-
z -----
3-CF3~phenyl
-CH 2 OC(=S)NMe-
z =
4- OCFi -ohenvl
j-ui^r^-pnenyi
-CH 2 OC(=S)NMe-
z =
3-Cl-phenyl
4-Cl-phenyl
-CH 2 OC(=S)NMe-
z =
3,5-diCl-phenyl
~y ivi c — unci 1 y i
-CH 2 OC(=S)NMe-
z =
4-Me-ohenvl
jjD-uuyie-pnenyi
-CH 2 OC(=S)NMe-
z =
2-naDhthalenvl
6-Me-2 -pyndiny l
-CH 2 OC(=S)NMe-
z =
4-Me-2-pyridinyl
*t s o-ujivic-z-pyriQ my 1
-CH 2 OC(=S)NMe-
z =
5-CF 3 -2-pyridinyl
J"J.vic-Z.-pj'IIUlllyl
-SCH 2 -
z =
2-Me-phenyl
^ ? j~uuvic-pnenyi
-SCH 2 -
z =
3-CF 3 -phenyl
4-CF3 -phenyl
-SCH 2 -
z =
4-Me-phenyl
4-/-Bu-phenyl
-SCH 2 -
z =
3-Cl-nhenvl
4-d-pnenyl
-SCH?-
z =
^~ivic-j-\^i-pnenyi
3-r-Bu-phenyl
-SCH 2 -
z =
2-naphthalenyl
1 -naDhthalenvl
-SCH 2 -
z =
3-pyridinyl
4-pyridinyl
-SCH 2 -
z =
6-Me-2-pyridinyI
5,6,7,8-tetrahydro-2-
naphthalenyl
-CH 2 0-N=C(SCH 3 >-
z =
3-CF 3 -phenyl
3-OCF 3 -phenyl
-CH 2 0-N=C(SCH 3 )-
z =
3-Me-phenyl
4-CF 3 -phenyl
-CH 2 0-N=C(SCH 3 )-
z =
4-OCF 3 -phenyl
4-Me-phenyl
WO 99/28305
PCT/US98/24265
107
Y
Column 1
Column 2
-CH 2 0-N=C(SCH 3 )-
j-v-i-pnenyi
3,5-diCl-phenyl
-CH 2 0-N=C(cyclopropyl)-
z =
j-CFo-nll^rivl
j-uui^-pnenyl
-CH 2 0-N=C(cyclopropyl)-
z =
3-^^e-nhpnvl
3 -phenyl
-CH 2 0-N=C(cyclopropyl)-
z =
4-OCF 3 -phenyl
4-Me-phenyI
-CH 2 0-N=C(cyclopropyl)-
z =
3-Cl-phenyl
3 5-diCl-nhenvl
Table 5b
= C1
Y
Column 1
column z
-O-
z =
Phenyl
j-LJlvie-pnenyl
-O-
z =
4-CF -5 -rVhenvl
3-Me-phenyl
-O-
z =
^ -F -nil n vl
3-(JCF 3 -pnenyl
-O-
z =
4-Me-ohenvl
j-i-pnenyl
-O-
z =
3-SCH-a -Dhenvl
2-Me-phenyl
-O-
z =
A CPU l _i
4-»(_i-i 3 -pnenyl
-O-
z =
3-cyclohexyl-phenyl
H-ovnr 2 -pncnyi
-O-
z =
6-CF'2-2-Dvridinvl
5-CF 3 -2-pyndiny 1
-O-
z =
4-CFo-2-r>vridiTivl
6-Me-2-pyridinyl
-o-
z =
6-(CF^CH / >OV4-nvriniidiTivl
j-ivie -^-py nuiny 1
-o-
z =
2-(CF^C^OV4-Dvrimidinvl
**-^r 3^ri2^-^-pynniiainyl
-o-
z =
4-Me-2-ovri di n vl
3,5-diMe-phenyl
-o-
z =
2-naphthalenyl
S 7 R.t;*tralwrttv\ 0
-?,o f / ,o-icuanyarO"Z-
uapnuiaicnyi
-o-
z =
4-OCF3-phenyl
j-t-D u-jjuciiy i
-o-
z =
4-f-Bu-phenyl
o-^r 3^x12*-^ -<£-pyrazinyi
-o-
z =
3-SCF3-phenyl
*r-o^r 3-pnenyi
-0-
z =
4-CF , *-6-Me-9-nvriHmv1
j-i^iN-pnenyi
-o-
z =
4. 6-dtN4e-2-Twri d i nvl
' » v uutiw ^ j_» y i luiiiy i
j , j -ai^i- r 3 ^-pneny 1
-o-
z =
5-Cl-2-thiazolyl
j-i-z-uiiazoiyi
-o-
z =
5-OCF 3 -2-thiazolyl
-0-
z =
5-CN-2-thiazolyl
5-SCH 3 -2-thiazolyl
-o-
z =
5-CF 3 -2-thiazolyl
4-Me-5-Cl-2-thiazolyl
-o-
z =
4-Me-5-I-2-thiazolyl
4-Me-5-CN-2-thiazolyl
-o-
z =
4-Me-5-CF 3 -2-thiazolyl
-0-
z =
3-(HC S C)-phenyl
3-(CH 3 C=C)-phenyl
-0-
z =
3-((CH 3 ) 3 CCsC)-phenyI
3-((CH 3 ) 3 SiG=C)-phenyl
WO 99/28305
PCTAJS98/24265
108
Y
Column 1
Column 2
-O-
Z =
3-( 0— CSQ-phenyl
5-Me-2-thienyl
-O-
Z =
5-(CH 3 ) 3 C-2-thienyl
5-Cl-2-thienvl 1
-O-
Z -
5-Br-2-thienyl
5-I-2-thienyl
-o-
Z =
4-Me-2-thienyl
-O-
Z =
4-Cl-2-thienyl
4-Br-2-thienvl
• M-JM A> UlJWllV 1
-o-
Z =
4-I-2-thienyl
t-,-? ULLYiC-Z-Ullcnyi
-o-
Z-
4-Me-5-Cl-2-thienyl
T~iTic~ j~r>i ~z.-Li iiciiyi
-o-
Z =
4-Me-5-I-2-thicnyl
-o-
Z =
5-Me-3-thienyl
-o-
Z =
5-Cl-3-thienyl
J Dr-j-iniciiyi
-o-
Z =
5-I-3-thienyl
• ivic~->~iniviiyi
-o-
Z =
4-(CH 3 ) 3 C-3-thienyl
-o-
Z =
4-Br-3-thienyl
4 - T— ^ — til i Am/1
■ » J tuicilyl
-o-
Z =
4,5-diMe-3-thienyl
4-Me-5-Pl-^-thi*»n\/l
-o-
Z =
4-Me-5-Br-3-thienyl
4-Me-S-T-^-tViif»tix/l
-o-
Z =
2-Cl-3-thienyl
±* w "i - pucuyi
-CH 2 0-
Z =
Phenyl
j"^ri -pncnyi
-CH 2 0-
Z =
2-Me-5-«-Pr-phenyl
2-Mp-4-OrHi -nh(»n\;l
^ "j-vxc-* t-w^xi^ "pnenyi
-CH 2 0-
z =
4-OCF-i-phenyl
-CH 2 0-
z =
3-OCHF 2 -phenyl
4-OCHFo-nhenvl
-CH 2 0-
z =
3,5-di(CF 3 )-phenyl
-CH 2 0-
z =
6-CF-j-2-pvridinvl
3-OPF-> -nhpnvl
-CH 2 0-
z =
4-CF 3 -2-pyridinyl
4> A/f a _ _.n\/T*i H t n \r 1
-CH 2 0-
z =
2-Me-4-OCF 3 -phenyl
j lvicx-py riumy i
-CH 2 0-
z =
3,6-diMe-2-pyridinyl
-2-nvridinvl
-CH 2 0-
z =
4,6-diMe-2-pyridinyl
vJ wv^r o -z.-pyriciinyi
-CH 2 0-
z =
4-CF 3 -6-Me-2-pyridinyl
3 -Me-2-nvri di n vl
-CH 2 0-
z =
4-Cl-2-pyrimidinyl
6- -nvri H i n\/l
-CH 2 0-
z =
4-Cl-2-pyrimidinyl
_P i-_n fi (*ti vl
-CH 2 0-
z =
2,6-diMe-4-pyridinyl
2,4,6-triMe-phenyl
-CH 2 0-
z =
3-Cl-2-pyridinyl
6-Cl-4-pyrimidinyl
-CH 2 0-
z =
1-napthalenyl
2,3,6-triMe-phenyl
-CH 2 0-
z =
6-Cl-2-pyrazinyl
4-CF3-2-pyrimidinyl
-CH 2 0-
z =
6-CF 3 -4-pyrimidinyl
2-i-Pr-phenyl
-CH 2 0-
z =
3-Me-2-pyridinyl
4-Cl-2-pyridinyl
-OCH 2 -
z =
2-Me-phenyl
2,5-diMe-phenyl
WO 99/28305
PCT/US98/24265
109
Y
■ Column 1
v^oiunin. z.
-OCH 2 -
Z =
3-CF 3 -phenyl
4-fT* -t -T*iKif»n\/1
-OCH 2 -
Z =
4-Me-phenyl
-o u-pneny i
-OCH 2 -
z =
3-Cl-nhenvl
H-ci-pnenyi
-OCH->-
z =
3-/-Bu-pnenyl
-OCH 2 -
Z =
2-n3phthalenyl
1 -naphthalenyl
-OCH 2 -
2 =
^-nvrirlinvl
•J pyiiuuiyi
4-pyridiny]
-OCH 2 -
Z =
6~A/fp— 7 -rvvri Hinvl
v X. JJJ' i iUUljr i
O /"< it "7 O
z-(5,o,7,5-
tetrahydro)naphthalenyl
-CH 2 0-N=C(CH 3 )-
z =
3 e-nh en v 1
'*-ci' 3 -pnenyl
-CH 2 0-N=C(CH?)-
z =
^ Hi TV_^£*_rth
<J 9 till VIC UIlCj lj' I
3-Cl-phenyl
-CH 2 0-N=C(CH 3 )-
z =
4- Rr-nh<Mi vl
3,5-di(CF 3 )-phenyl
-CH 2 0-N=C(CH 3 )-
z =
4-/-Bu-phenyl
-CH 2 0-N=C(CH 3 )-
z =
5-CF 3 -2-pyndiny 1
-CH 2 0-N=C(CH 3 )-
z =
4-OCFi -nhpnvl
3-OCHF 2 -phenyl
-CH 2 0-N=C(CH 3 )-
z =
S — Tvff* — "7 — n vri H i n \j 1
4-Cr 3 -6-Me-2-pyndinyl
-CH 2 0-N=C(CH 3 )-
z =
4— Ivf f* — 7 — T\ VT*i H i
■ j^yiiLiuiy i
4,6-diMe-2-pyridinyl
-CH 2 0-N=C(CH^)-
z =
u ivic-^-pyntiiiiyi
6-CF 3 -2-pyridinyI
-CH 2 0-N=C(CH 3 )-
z =
6-OMe-2-pyridinvl
J fi—Hi\^P— A\-,xwrr\t\
-CH 2 0-N=C(CH 3 )-
z =
2 6-diCI-4-nvridinvl
O-LiUr 3-z-pynainyI
-CH 2 0-N=C(CH 3 )-
z =
4-0!\4e-2-nvriHinvl
H-ULr 3 -z-pynainyl
-CH 2 0-N=C(CH 3 >
z =
5-OCH K^-^-fwriHitwl
^/ ^ JjyilUUlyl
O-ULr 3-x-pynainyl
-CH 2 0-N=C(CH 3 >
z =
4-OCHF^ -nvriH in vl
->-( i Cr3CH2U)pnenyl
-CH 2 0-N=C(CH 3 )-
z =
n-OCHFi - 9 -twri Hinwl
3-Et-phenyl
-CH 2 0-N=C(CH 3 )-
z =
1,2,3,4- tetrahydro-2-
uapjiina leny I
-CH 2 0-N=C(CH 3 )-
z =
3 -ethynylpheny 1
-CH 2 0-N=C(CH 3 )-
z =
f-Bu
z-r o-^r 3 -pnenyl
-CH=N-OCH(CH 3 )-
z =
4-CFi-ohenvl
1 PC* nkantrl
J-Lr 3-pnenyi
-CH=N-OCH(CHq)-
z =
4-OCF-j -nhenvl
3-(JL>r3-pnenyl
-CH=N-OCH(CH-»)-
z =
j wi pncnyi
4-Cl-phenyl
-CH=N-OCH(CH 3 )-
z =
3,5-diCl-phenyl
3 , 5 -dif CF^i Vohenvl
-CH=N-OCH(CH 3 >
z =
3-Me-phenyl
4-Me-phenyl
-CH=N-OCH(CH 3 )-
z =
2-naphthalenyl
4-OCHF 2 -phenyl
-CH=N-OCH(CH 3 )-
z =
3-OCHF 2 -phenyl
4-CF 3 -2-pyridinyl
-CH=N-OCH(CH 3 )-
z =
5-CF 3 -2-pyridinyl
6-CF 3 -2-pyridinyl
-CH=N-OCH(CH 3 )-
z =
4-Me-2-pyridinyI
5-Me-2-pyridinyl
-CH=N-OCH(CH 3 )-
z =
6-Me-2-pyridinyl
4-CF 3 -6-Me-2-pyridinyl
WO 99/28305
PCT/US98/24265
110
Y
Column 1
-CH=N-OCH(CH 3 >
z =
D-vJCr 3-Z-pynainyl
-CH=N-OCH(CH 3 )-
z =
6-OCF 3 -2-pyridinyl
fuuiir 2 ^ pynuinyi
-CH=N-OCH(CH 3 )-
z =
— ' 7 ^ JjyXXUXliyi
o-uL^rir o-^-pynuinyi
-CH=N-OCH(CH 3 )-
z =
3 - /-Bu-pheny 1
*T-t -D u-p neny i
-CH 2 -SC(Et)=N-
z =
4- CFi -nlipnvl
3 -i_r 3 -pnenyl
-CH 2 -SC(Et)=N-
z =
4-OCF-5 -Dhenvl
-CH 2 -SC(Et)=N-
z =
3-Cl-ohenvl
*f-ci-piienyi
-CH 2 -SC(Et)=N-
z =
3 5-diPI-nhpnvl
3,5-ai(Cr3)-pnenyJ
-CH 2 -SC(Et)=N-
z =
3 -nh pnvl
4-Me-phenyl
-CH 2 -SC(Et)=N-
z =
— ' j — ' uii vxv jjiicji y J
z-napntnalenyl
-CH 2 -SC(Et)=N-
z =
o~iviC"*t -pyriQiny i
4-Me-2-pyndinyl
-CH 2 -SC(Et)=N-
z =
4 6-dift4e-2-nvridinvl
j-d-z-pynainyl
-CH 2 -SC(Et)=N-
z =
"r , u-luv—j -z,- py riciuiy i
5-Me-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
j v^x "J "X-py i iuiiiyi
5-iir-o-Me-2-pynainy]
-CH 2 -SC(=S)NMe-
z =
-nhenvl
• v^x -Z jjuciiy i
3-Ct*3-pnenyl
-CH 2 -SC(=S)NMe-
z =
» v-"wr ^-piiwixyi
3 -UCr 3 -pnenyl
-CH 2 -SC(=S)NMe-
z =
3-C1-nhenvI
4- d -pnenyl
-CH 2 -SC(=S)NMe-
z =
3 5-diC1-nhf>nvl
J ,3 -ai(Cr 3)-pnenyl
-CH 2 -SC(=S)NMe-
z =
3 - M^-nli f*r»vl
•-' IV AW |JXlSXiy 1
4-Me-phenyl
-CH 2 -SC(=S)NMe-
z =
3 S~fii ^/f P— rvV)pri\/l
•J <>-J Uilrlb piiciiyi
2-naphthalenyl
-CH 2 -SC(=S)NMe-
z =
o— A/Tf^-^— "n\/rirlirT\/1
w ivit Ljyuujiiyi
4-Me-2-pyridinyl
-CH 2 -SC(=S)NMe-
z =
4 6-di\fe-2-nvridinv1
j - v^i-z-pyriuinyj
-CH 2 -SC(=S)NMc-
z =
4 6-diCl-2-Dvridinvl
* j v uivi y i xuxxxy i
5-lVle -2-p3indiny 1
-CH 2 -SC(=S)NMe-
z =
5-CF'>-2-nvridinv1
j-rir- o-JVie-^-pynuiny 1
-CH 2 SC(SMe)=N-
z =
3 -Me-phenyl
*T-ivxc-pnenyi
-CH 2 SC(SMe)=N-
z =
3 . 5-diMe-nhen vl
j-^i-pnenyi
-CH 2 SC(SMe)=N-
z =
4-C1 -nhen vl
j,D-uiL-i-pnenyi
-CH 2 SC(SMe)=N-
z =
3-CF'5-nhenvl
*f -i_-r 3 -pnenyi
-CH 2 SC(SMe)=N-
z =
3-OCFi -Dhenvl
*t-v_^*w. -pnenyi
-CH 2 SC(SMe)=N-
z =
3 5-dif'CF'iVnhenvl
^ri2^"2
-CH 2 SC(SMe)=N-
z =
f-Bu
2-nap hthaleny 1
-CH 2 SC(SMe)=N-
z =
6-Me-2-pyridinyl
4-Me-2-pyridinyl
-CH 2 SC(SMe)=N-
z =
4,6-diMe-2-pyridinyl
5-Cl-2-pyridinyl
-CH 2 SC(SMe)=N-
z =
4,6-diCl-2-pyridinyl
5-Me-2-pyridinyI
-CH 2 SC(SMe)=N-
z =
5-CF 3 -2-pyridinyl
5-Br-6-Me-2-pyridinyl
-CH 2 S-
z =
2-Me-phenyl
3-CF3-phenyl
-CH 2 S-
z =
4-CF 3 -phenyl
2,5-diMe-phenyl
WO 99/28305
PCT/US98/24265
111
Y
Column 1
column z
-CH 2 S-
Z =
2-Et-phenyl
j -v-4-pneny i
-CH 2 S-
Z =
2-Cl-Dhenvl
z,j-aici-pnenyi
-CH 2 S-
Z =
4,6-du\4e-2-nvrimidinvl
H-ivie- x,z,4-inazoi-3-yl
-CH 2 S-
Z =
2-naphthalenyI
l-R4e-2-imidazolyl
-CH 2 S-
Z =
4-\4f^- 2 -nvri m iHin\/l
~ i'iV At ^/jr i iiiuuuiyi
5-Me- 1 ,3,4-tniadiazol-2-yl
-CH 2 0-N=C(CH 3 )CH 2 S-
Z =
— ' J.VJL& — VI
2-Me-phenyl
-CH 2 0-N=C(CH 3 )CH 2 S-
Z -
4-Cr 3 -pnenyI
-CH 2 0-N=C(CH 3 )CH 2 S-
Z =
3-Cl-nhenvl
z-fct-pnenyl
-CH 2 0-N=C(CH 3 )CH 2 S-
Z =
4-Cl-nhpnvl
2-naphthalenyl
-CH 2 0-N=C(CH,)CH 9 S-
z =
y S_ HlX>f nlipmrl
4-CF 3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
^-\4f*-T\h pnvl
2-Me-phenyl
-CH 2 0-N=C(CH*)CH->0-
z =
Zl_\/f r»_r\l^ £>rt\/1
3-CF 3 -phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4— f^F*^ *nnpTi\/]
4-Cl-pnenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
3-Cl-Dhenvl
j,j-aiMe-pnenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
2 5-diMe-nhpm/l
2-Me-5-i-Pr-phenyl
-CH 2 O-N=C(CH 3 )CH 2 0-
Z =
3-Et-phenyl
6-CF3 -2-pyndinyl
-CH 2 0-N=C(CH 3 )CH 2 0-
Z =
4-CF < a-2-Dvridinvl
-z-pyndinyl
-CH 2 0-N=C(CH 3 )CH 2 O-
z =
6-Me-2-pyridinyl
5-Me-2 -pyridiny 1
-CH 2 0-N=C(CH 3 )CH 2 O-
z =
4-Me-2 -pyridiny 1
l -ilapilUialcIlyl
-CH 2 0-N=C(CH 3 )CH 2 O-
z =
2-naohthal en vl
2-CF^ -phenyl
-CH 2 CH 2 -
z =
2-Me-nhenvl
2,5- diMe-pheny 1
-CH 2 CH 2 -
z =
3-CF3 -phenyl
*t-^ r 3 -pneny j
-CH 2 CH 2 -
z =
3-Cl-phenyl
4— t 1 — Tlh^HX/l
-CH 2 CH 2 -
z =
3-OCF3-phenyl
-CH 2 CH 2 -
z =
2-Et-phenyl
^-ivic-j-v-i-pncnyi
-CH 2 CH 2 -
z =
2-naphthalenyl
3,6-diMe-2-pyndinyl
-CH=C(CH 3 )-
z =
3-^^e-nhenvl
4-Me-phenyl
-CH=C(CH 3 )-
z =
3.5-diMe-ohenvl
j-^i-pnenyi
-CH=C(CH 3 )-
z =
4-Cl-phenyl
j-vy^r^-pnenyi
-CH=C(CHi)-
z =
3-Cr3-pnenyI
-CH=C(CH 3 )-
z =
4-CF 3 -phenyl
2-naphthalenyl
-CH=C(CH 3 >
z =
4-CF 3 -2-pyridinyl
6-CF3 -2-pyridinyl
-CH=N-N=C(CH 3 )-
z =
3-Me-phenyl
4-Me-phenyl
-CH=N-N=C(CH 3 )-
z =
3-CF 3 -phenyl
4-CF3-phenyl
-CH=N-N=C(CH 3 )-
z =
3-OCF 3 -phenyl
4-OCF 3 -phenyl
-CH=N-N=C(CH 3 )-
z =
3,5-diMe-phenyl
3-Cl-phenyl
-CH=N-N=C(CH 3 )-
z =
4-Cl-phenyl
3,5-diCl-phenyl
WO 99/28305
PCT/US98/24265
112
Y
r^nlnmr* 1
Column 2
-CH=N-N=C(CH 3 )-
z =
4— l^F-^ -/»iwriHim/1
*T 3 r luiiiy 1
5-Cr3-2-pyndinyl
-CH=N-N=C(CH 3 )-
Z =
n— l^F-^ •7-nvT'inim/l
\j \— j. j "*i~pyi lUliiy 1
4-Me-2 -pyridiny I
-CH=N-N=C(CH,)-
z =
>Mfi- 7— rwriHin\/l
6-Me-2-pyridinyl
-CH=N-N=C(CH 3 )-
z =
2-nanhthalprivl
4,o-aiMe-2-pynainyl
-CH=N-N=C(CH 3 )-
Z -
^-P t— nhpnvl
j x-ri-jjiicxiyi
?-Bu
-CH 2 0-N=C(CH 3 )C(=NOCHi)-
z =
^-TVf p-nhfnvl
ivic puciiy i
4-Me-phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH,)-
z =
j , -? -uiivic -pncny l
3-CI-pnenyl
-CH 2 0-N<:(CH-»)C(=NOCH*V
z =
*t- w i-pneny i
3,5-diCl-phenyl
-CH 2 O-N=C(CH 3 )C(=NOCHi0-
z =
4-CF 3 -phenyl
-CH 2 0-N=C(CH 3 )C(=NOCHO-
z =
3 < !-Hiff' , F*»W»hpTi\/l
3-OCF 3 -phenyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
~ wv^i 3-piiciiyi
CH 3
-CH 2 0-N=C(CH,)C(=NOCHi )-
z =
f-Bu
2-naphthalenyl
-CH 2 0-N=C(CH 3 )C(=NOCH,V
z =
u-pneny i
4-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCHo>
z =
j ivic-^-pyriumyi
6-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 >
z =
4-l!F-> -2— nvriHitivl
■ 3 pyuuuiyi
5-Cr 3 -2-pyndinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
o-{jF*> -2— nvrirlinvl
*■* v^a j pyiiuuiyi
4,o-aiMe-2-pyndinyl
-CH 2 0-N=C(CH 3 )C(=NOCH,)-
z =
• pyrunicuiiyi
6-CF 3 -2-pjTimiduiyl
-CH=N-N(CH 3 )-
z =
3 - pnv 1
4-Me-phenyl
-CH=N-N(CH 3 )-
z -
3 5-dilVff*-nhf»nvl
j-L-i-pnenyl
-CH=N-N(CH 3 )-
z =
4-Cl-DhenvI
j,j-on^i-pnenyj
-CH=N-N(CH 3 )-
z =
w*. ■* |jiiwuyi
4-L.r 3 -pnenyl
-CH=N-N(CH 3 )-
z =
3-OCF->-nhenvl
wur 3 -pnenyl
-CH=N-N(CH 3 )-
z =
2 -nanhth a 1 ptivI
^-/-iju-pnenyj
-CH=N-N(CH 3 )-
z =
4 — \n P — "7 -nuri rl i n a /l
> xvj.t~i*"pyiiuiiiyi
5-Me-2-pyridinyl
-CH=N-N(CH 3 )-
z =
-nuri H i r\\A
4-Cr 3 -2-pynainyl
-CH=N-N(CH 3 )-
z =
\~>i j. ^."pynuuiyi
o-Cr 3 -2-pyndiny 1
-CH=N-N(CH-»V
z =
n i ,u-uMvic-^-pyriuiiiyi
4-CF 3 -2-pynmidinyl
-CH 2 OC(SMe)=N-
z =
4- CF-> -nhpnvl
3-CF 3 -phenyl
-CH 2 OC(SMe)=N-
z =
J -ULr 3 -pnenyl
-CH 2 OC(SMe)=N-
z =
3-CI-nhenvl
H-ui-pnenyl
-CH 2 OC(SMe)=N-
z =
3,5-diCl-phenyl
3-Me-phenyl
-CH 2 OC(SMe)=N-
z =
4-Me-phenyl
3,5-diMe-phenyl
-CH 2 OC(SMe)=N-
z =
2-naphthalenyl
6-Me-2-pyridinyl
-CH 2 OC(SMe)=N.
z =
4-Me-2-pyridinyl
4,6-diMe-2-pyridinyl
-CH 2 OC(SMe)=N-
z =
5-CF 3 -2-pyridinyl
5-Me-2-pyridinyl
-CH 2 OC(=S)NMe-
z =
4-CF 3 -phenyl
3-CF 3 -phenyl
-CH 2 OC(=S)NMe-
z =
4-OCF 3 -phenyl
3-OCF 3 -phenyl
WO 99/28305
PCT/US98/2426S
113
Y
■ Column 1
Column 2
-CH 2 OC(=S)NMe-
Z =
3-Cl-phenyl
4-Cl-nhenvl
-CH 2 OC(=S)NMe-
Z =
3,5-diCl-phenyl
3-Me-phenyl
-CH 2 OC(=S)NMe-
z =
4-Me-phenyl
3 S-HiA^f^-nfiPnvl
-CH 2 OC(=S)NMe-
z =
2-naphthalenyl
n-\'f f^-?-nvriHi ttv/1
-CH 2 OC(=S)NMe-
z =
4-Me-2-pyridinyl
4 6-diMe-2-nvrirfiTivt
-CH 2 OC(=S)NMe-
z =
5-CF^-2-pyridinyl
5 -l^G-2-nvri rf i n vl
-SCH 2 -
z =
2-Me-phenyl
2.5-diMe-r>henvl
-SCH 2 -
z =
3-CF 3 -phenyl
4-CF 3 -phenyl
-SCH 2 -
z =
4-Me-phenyl
4-/-Rn -n h pn vl
-SCH 2 -
z =
3-Cl-phenyl
~ wi-puciiyi
-SCH 2 -
z =
2-Me-5-Cl-phenyl
3 -/-Bu-phenyl
-SCH 2 -
z =
2-naphthalenyl
1 -naphthalenyl
-SCH 2 -
z =
3-pyridinyl
4-pyndinyl
-SCH 2 -
z =
6-Me-2-pyridinyl
-3,o s /,o-ieLranyuro-z-
naphthalenyl
-CH 2 0-N=C(SCH 3 )-
z =
3-CF 3 -phenyl
j-u\^r 3 -pnenyi
-CH 2 0-N=C(SCH 3 )-
z =
3 -Me-phenyl
*r-v- r* 3 -pnenyi
-CH 2 0-N=C(SCH 3 )-
z =
4-OCF 3 -phenyl
4-Me-phenyl
-CH 2 0-N=C(SCH 3 )-
z =
3-Cl-nhenvl
■?,D-oid-pnenyI
-CH 2 0-N=C(cyclopropyl)-
z =
3-CF 3 -phenyl
-CH 2 0-N=C(cyclopropyl)-
z =
3-Me-phenyl
-CH 2 0-N=C(cyclopropyl)-
z =
4-OCF 3 -phenyl
4-Me-phenyl
-CH 2 0-N=C(cyclopropyl)-
z =
3-Cl-phenyl
3,5-diCl-phenyl
Table 5c
= CF 3
Y
Column 1
Column 2
-O-
z =
Phenyl
3-OMe-phenyl
-0-
z =
4-CF 3 -phenyl |
3-Me-phenyl
-0-
z =
3-F-phenyl
3-OCF 3 -phenyl
-0-
z =
4-Me-phenyl
3-I-phenyl
-O-
z =
3-SCH 3 -phenyl
2-Me-phenyl
-O-
z =
3-SCHF 2 -phenyl
4-SCH 3 -phenyl
-O-
z =
3 -cyclohexyl-phenyl
4-SCHF 2 -phenyl
-O-
z =
6-CF 3 -2-pyridinyl
5-CF 3 -2-pyridinyl
-O-
z =
4-CF 3 -2-pyridinyl
6-Me-2 -pyridinyl
WO 99/28305
PCT/US98/24265
114
Y
Column 1
WUlUillll .Z.
-O-
z =
6-(CF3CH20)-4-pyrimidinyl
-O-
z =
2-(CF 3 CH20)-4-pyrimidinyl
4-C CFo CHi OV?-nvrim i Hi m;1
-O-
z =
4-Me-2-pyridinyl
\ .HiAnO-nnamrl
j-uiivic-pneiiyi
-O-
z =
2-naphthalenyl
5 6 7 8-tetrahvr1rn-9-
nnnntniilpnvl
iiapiiuialdiy 1
-O-
z =
4-OCF3-phenyl
^_/_"Rll_r\h» : »r>'\/1
-O-
z =
4-/-Bu-phenyl
o-v ^ r 3 ^n2^ -z-py raziny 1
-O-
z =
3-SCFrj-ohenvl
*f-^L.r 3-pnenyi
-O-
z =
4-CFi -6-Me-2-nvrir1invl
j-^JN-pnenyi
-O-
z =
^,!>-ai(Cr3)-pneny]
-o-
z =
5-Cl-2-thiazolyl
j-i-z-miazoiyi
-0-
z =
5-(CH 3 ) 3 Si-2-thiazolyl
-0-
z =
5-CN-2-thiazolyl
-0-
z =
5-CF 3 -2-thiazolyl
4-Me-5-Cl-2-thiazolyl
-o-
z =
4-Me-5-I-2-thiazolyl
4-Me-5-CN-2-thiazolyl
-o-
z =
4-Me-5-CF3-2-thiazolyl
-O-
z =
3-(HC=C)-phenyl
3-(CH 3 C=C)-phenyl
-o-
z =
3-((CH 3 ) 3 COC)-phenyl
3-((CH 3 ) 3 SiCsC)-phenyl
-o-
z =
3-([>— C=Q-phenyl
5-Me-2-thienyl
-o-
z =
5-(CH3)3C-2-thienyl
j-wi-z-uucnyi
-o-
z =
5-Br-2-thienyl
S-T-?-thif*nvl
-o-
z =
4-Me-2-thienyl
t-^i^ X13 73 ^-'■-^■uiienyi
-o-
z =
4-Cl-2-thienyl
4._"Rr_7_thif»n\/1
-o-
z =
4-1-2-thienyl
■ j j-uiivic-z-tnienyi
-o-
z =
4-Me-5-Cl-2-thienyl
t-ivie- z> -or-z-imeny 1
-o-
z =
4-Me-5-I-2-thienyl
-> -v^i-z - uxicny 1
-o-
z =
5-Me-3-thienyl
j J13 )2^-j -tnieny J
-o
z =
5-Cl-3-thienyl
s> -jji- j-Liueiiyi
-o-
z =
5-I-3-thienyl
*t-ivic-_>- inicnyi
-o-
z =
4-(CH 3 ) 3 C-3-thienyl
4-Cl-3-thienyl
-o-
z =
4-Br-3-thienyl
4-I-3-thienyl
-O-
z =
4,5-diMe-3-thienyl
4-Me-5-Cl-3-thienyl
-o-
z =
4-Me-5-Br-3-thienyl
4-Me-5-I-3-thienyI
-o-
z =
2-Cl-3-thienyl
2-CF3~phenyl
CH 2 0-
z =
Phenyl
3-CF3-phenyl j
CH 2 0-
z =
2-Me-5-/-Pr-phenyl
2-Me-4-OCH 3 -phenyl
WO 99/28305
PCT/US98/24265
115
Y
Column 1
PnliiniTi 0
V— .VJllXIllil -Z.
-CH 2 0-
Z =
4-OCF 3 -phenyI
x-ivic--)-\^r2 -pncnyi
-CH 2 0-
Z =
3-OCHF 2 -phenyl
4- OPHF^ -nhpnvl
H-wLiiir 2 -piicuyi
-CH 2 0-
Z =
3 5-di(CF?")-Dhenvl
x-ivie-H-vy^ri_r2~pnenyi
-CH 2 0-
z =
6-CFo -2-nvridinvl
j-^cr^-pnenyi
-CH 2 0-
z =
4-C!!F'>-2-TivTiHinvl
4-Me-2 -pyndinyl
-CH 2 0-
z =
2-Me-4-OPF'» -nhpnvl
5 -Me -2-pyrid inyl
-CH 2 0-
z =
3 6-di^fe-2-TwririiTiv1
5 - CF^ -2-pyndiny 1
-CH 2 0-
z =
4 f\-(\V\A P—~) ~Twir\f\ in\/l
o-Utr 3 -2-pyndiny 1
-CH 2 0-
z -
4-CF*i -tfWJvfp-^-nvTiHinvl
3-MeT2-pyndinyl
-CH 2 0-
z =
4— PI— *7— n\7f*1tnt/^invl
~ £m-y)y\ iiiiiuiiiyi
6-Me-2-pyridinyl
-CH 2 0-
2 -
*t v^i x-pynmitiiiiyi
3-bt-pnenyl
-CH 2 0-
z =
» ° uuvic"*t -pynu uiyi
2,4,6-triMe-phenyl
-CH 2 0-
z =
3 -P 1 - -ti vri H i ¥i \/ 1
6-Cl-4-pyrimidinyl
-CH 2 0-
z =
1 -nuntVi nl/^TiT/l
1 ilaLFUlalCXiyj.
2, J ,o-tnMe-pnenyl
-CH 2 0-
z =
6-P 1 - ^ -nvra7inv1
4-Cr 3 -2-pynmiainyl
-CH 2 0-
z =
6— PFi — 4-r> vrri m i H in vl
v j ™ j^y i inuumy i
2-/-Pr-phenyl ■
-CH 2 0-
z =
3-\4e-2-nvriHi'Tvvl
s «iv a> y 1 lUUiy 1
4-Cl-2-pyndinyl
-OCH 2 -
z =
^ lYiw ijiiciiy i
2,5-diMe-phenyl
-OCH 2 -
z =
3-CF3 -phenyl
4-CF 3 -phenyl
-OCH 2 -
z =
4— Me-nh envl
4 *-(-i3u-pnenyi
-OCH 2 -
z =
3-Pl-nhf»nvl
j unci ly 1
4-Cl-pnenyi
-OCH 2 -
z =
?-M'f»-S_Pl-nh*»nv1
x— ivic-j— \^i-piienyi
3-/-i5u-pnenyI
-OCH 2 -
z =
2-nanhthal en vl
1 -naphthalenyl
-OCH 2 -
z =
3 -11 vri rfi nv 1
4-pyndinyl
-OCH 2 -
z =
6-^^e-2-nvri Hi n vl
tetrahydro)n0plithalenyl
-CH 2 0-N=C(CH->)-
z =
iviciyiiciiyi
4-Cr*3-pnenyi
-CH 2 0-N=C(CH-j)-
z =
3 HiA^#*_nnf»nv1
-j j •j-uuvic-piioiiyi
3-Cl-phenyl
-CH 2 0-N=C(CHi)-
z =
4— Ttr-nhfvnvl
• jji~jjuciiy i
J,j-ai^Cr 3 ^-ptienyl
-CH 2 0-N=C(CH 3 )-
z =
4-f-Bu-phenyl
-CH 2 0-N=C(CH 3 >
z =
3-f-Bu-phenyl
5i -PF"* H i nvl
V*>J j -A-py A 1UU1Y 1
-CH 2 0-N=C(CH 3 )-
z =
4-OCF 3 -phenyl
3-OCHF 2 -phenyl
-CH 2 0-N=C(CH 3 )-
z =
5-Me-2-pyridinyI
4 -CF 3 -6-Me-2 -pyndinyl
-CH 2 0-N=C(CH 3 )-
z =
4-Me-2-pyridinyl
4,6-diMe-2-pyridinyl
-CH 2 0-N=C(CH 3 )-
z =
6-Me-2~pyridinyl
6-CF 3 -2-pyridinyl
-CH 2 0-N=C(CH 3 )-
z =
6-OMe-2-pyridinyl
2,6-diMe-4-pyridinyl
-CH 2 0-N=C(CH 3 )-
z =
2,6-diCl-4-pyridinyl
5-OCF 3 -2-pyridinyl
WO 99/28305
PCT/US98/24265
116
Y
Column 1
-CH 2 0-N=C(CH,)-
Z =
4-OMe-2-nvridinv1
^t-UCr 3-z-pynamyi
-CH 2 0-N=C(CH 3 )-
Z =
5-OCHFT-2-Dvridinvl
o-ULr o-z-pyouinyi
-CH 2 0-N=C(CH 3 )-
Z =
4-OCHF 2 -pyridinyl
j-^cr 5 >^*T-2 /P«cnyi
-CH 2 0-N=C(CH 3 )-
Z =
6-OCHF-)-2-nvridinvl
3-Et-phenyl
-CH 2 0-N=C(CHo)-
Z =
1 -naiVhrtinlpm/l
x ua^ii uialGIiy 1
l,2,3,4-tetranydro-2-
naphthalenyl
-CH 2 0-N=C(CHn>)-
Z =
3-ethynylphenyl
-CH 2 0-N=C(CH 3 )-
Z =
f-Bu
^-r-j-t,r 3 -pnenyi
-CH=N-OCH(CH 3 )-
z =
4-CF->-nhenvl
o-Cr 3 -pnenyl
-CH=N-OCH(CH 3 )-
Z =
4-OCF-> -nhenvl
j-ULr 3 -pnenyl
-CH=N-OCH(CH 3 )-
z =
4-Cl-pnenyl
-CH=N-OCH(CH 3 )-
z =
3 5-diCl-nhenvl
o,5-ui(Cr 3 )-pneny I
-CH=N-OCH(CH 3 )-
z -
^ -\/f e-nVi pnv1
4-Me-phenyl
-CHNN-OCHfCH^)-
z =
2-nanhthalpnvl
< +-vjcxir2-pnenyl
-CH=N-OCH(CH 3 )-
z =
3-OCHFi-nhenvl
i-L.r 3 -^-pynainyl
-CH=N-OCH(CH 3 )-
z =
j \~?r 3 -z -pynainyi
0-CF3 -2-pynainyl
-CH=N-OCH(CH^)-
z =
4-Jvle-2-TYvririiTivI
r itav A> \'J i IMI 1 IJf 1
5-Me-2-pyndinyl
-CH=N-OCH(CH 3 )-
z =
vr x. ij y i ivjiii y l
f-t-r 3 -o-ivie-2-pynclinyl
-CH=N-OCH(CHi)-
z =
3 -2-pyndinyl
-CH=N-OCH(CH 3 )-
z =
6-OCFi -2-T>vridinvl
1 vjv^rw 2"^--pynainyl
-CH=N-OCH(CH 3 )-
z =
o-ULUr 2 -z-pynainyl
-CH=N-OCH(CHo)-
z =
3-/-Bu-phenyl
*t ■* -r> u-pncny 1
-CH 2 -SC(Et)=N-
z =
4-CF-2 -ohenvl
j v^r a-pnenyi
-CH 2 -SC(Et)=N-
z =
4-OCFi-Dftenvl
j'ULr 3 -pnenyi
-CH 2 -SC(Et)=N-
z =
3-Cl-phenyl
*t ■ "pnciiy 1
-CH 2 -SC(Et)=N-
z =
3,5-diCl-ph.enyl
jj^-ui^v^r^j'pnenyi
-CH 2 -SC(Et)=N-
z =
3-Me-ohenvl
t-ivie-pnenyi
-CH 2 -SC(Et)=N-
z =
3.5-diMe-nhenvl
^~napniiiaiciiyi
-CH 2 -SC(Et)=N-
z =
fi— -T*\/T"i /"iin\/1
u iviv-x-^yi luiiiyi
4-Me-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
4 6-diM^e-5-nvrirfinv1
■ s w uuviv l/ y a luuiy i
j-w-i-x-pynuinyl
-CH 2 -SC(Et)=N-
z =
4,6-diCl-2-pyridinyl
5-Me-2-pyridinyl
-CH 2 -SC(Et)=N-
z =
5-CF3-2-pyridinyl
5-Br-6-Me-2-pyridinyl
-CH 2 -SC(=S)NMe-
z =
4-CF 3 -phenyl
3-CF 3 -phenyl
-CH 2 -SC(=S)NMe-
z =
4-OCF 3 -phenyl
3-OCF 3 -phenyl
-CH 2 -SC(=S)NMe-
z =
3-Cl-phenyl
4-Cl-phenyl
-CH 2 -SC(=S)NMe-
z =
3,5-diCl-phenyl
3,5-di(CF 3 )-phenyl
-CH 2 -SC(=S)NMe-
z =
3-Me-phenyl
4-Me-phenyl
WO 99/28305
PCT/US98/24265
117
Y
• Column 1
V -hi 1 1 1 1 1 1| ^
-CH 2 -SC(=S)NMe-
Z =
3 5-diMe-nhenvl
^-napiiuiaienyi
-CH 2 -SC(=S)NMe-
Z =
6-Me-2-ovridinvl
*t-ivic - ^ -pynamy 1
-CH 2 -SC(=S)NMe-
Z =
4 , 6-diMe-2-pyridiny 1
^ - C 1 - 9 -n vri r4 i n v 1
-CH 2 -SC(=S)NMe-
Z =
4,6-diCI-2-pyridinyl
S — nn f* ~ 7 _ T"fc \ ^ n *1 ■ n ^ / 1
•J -1VXG— X— LJjr 11L1II1Y 1
-CH 2 -SC(=S)NMe-
z -
5-CF3-2-pyridinyl
^_'Rr_f\_'\/f*a_'>_rwT*iH4nx/1
j -x>i - D-ivic""ji~py noiny i
-CH 2 SC(SMe)=N-
Z =
3 -Me-pheny I
A _lvT ^.nnpnvl
*T — 1VI C— JJ UG1 i y 1
-CH 2 SC(SMe)=N-
z =
j-^i-pnenyi
-CH 2 SC(SMe)=N-
z =
4-C 1-ohenvl
j , j -ui^i-pnenyi
-CH 2 SC(SMe)=N-
z =
3-CF^ -r>henvl
t-v^r^-pnenyi
-CH 2 SC(SMe)=N-
z =
3-OCF 3 -phenyl
"t-wv^jt 3 P"Ciiyi
-CH 2 SC(SMe)=N-
z =
3,5-di(CF 3 )-phenyl
V-'l JLyV_-I in I iJ Li
-CH 2 SC(SMe)=N-
z =
/-Bu
z,-iid.pnuidiciiy i
-CH 2 SC(SMe)=N-
z =
6-Me-2-rwridinvl
t- lvic-x -pynamy i
-CH 2 SC(SMe)=N-
z =
4,6-diMe-2-pyridinyl
S - f** 1 - "7 -n vri H i nvl
-CH 2 SC(SMe)=N-
z =
4 6-diCl-2-nvridinvl
.? ■"ivie-z-py nainy 1
-CH 2 SC(SMe)=N-
z =
5 -CF^ -2-pyridiny 1
S — R r— fi— IVAa - 7 — nun ti i r»x / 1
J jOI «J 1V1C "yilU-lIlyi
-CH 2 S-
z =
2-Me-nhenvl
3-CF^ -phenyl
-CH 2 S-
z =
4-CF'j-nhenvl
2j5-di\Ie-phenyl
-CH 2 S-
z =
2-Et-phenyl
o v^-i piiciiyi
-CH 2 S-
z =
2-Cl-t>heiw1
z,j-Qi^i-pncnyi
-CH 2 S-
z =
4. 6- diMe - 2-nvrim i d i n vl
*t-lVlc- 1 jZ.jH-lTlaZOl- j-yi
-CH 2 S-
z =
2-naphthalenyl
l "ivj.c— dC-lilliUd^UJ y 1
-CH 2 S-
z =
4-Nle-2-nvrimidinvl
J-iVIC-1, JjH-UUttUlaZOi-^-yi
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
3-Me-phenyl
^> 1VJLC— |J11CJ1J^ 1
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
3-CF 3 -phenyl
■ v^i T HixClljrl
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
3-Cl-phenyl
9 -T^ t_nVi ptv\i 1
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
4-Cl-phenyl
ii apnuiaicny i
-CH 2 0-N=C(CH 3 )CH 2 S-
z =
2,5-diMe-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
3 -Me-pheny 1
^.-ivic -puciiy l
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4-\flf*-nliPfYvl
3-CF^ -phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4-CF 3 -phenyl
4-Cl-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
3-Cl-phenyl
3,5-diMe-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
2,5-diMe-phenyl
2-Me-5-/-Pr-phenyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
3-Et-phenyl
6-CF3-2-pyridinyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4-CF3-2-pyridinyl
5-CF3 -2-pyridinyl
-CH 2 0-N=C<CH 3 )CH 2 0-
z =
6-Me-2-pyridinyl
5-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )CH 2 0-
z =
4-Me-2-pyridinyl
l-naphthalenyl
WO 99/28305
PCT/US98/24265
118
Y
Column 1
V • \I l UX 1 1 1 1
-CH 2 O-N=C(CH 3 )CH 2 0-
Z =
2-naphthalenyl
-^-v_,r ^ pncnyi
-CH 2 CH 2 -
Z =
2-Me-phenyl
2 , 5 -diMe-p heny 1
-CH 2 CH 2 -
Z =
3-CF-a -Dhenvl
^-v^r^-pnenyi
-CH 2 CH 2 -
Z =
3-Cl-phenyl
*t ~ k> i |iiiciiy i
-CH 2 CH 2 -
Z =
3-OCF 3 -phenyl
*t-«-/v^r j-pncnyi
-CH 2 CH 2 -
Z =
2-Et-phenyl
.t. -ivic-_?-i^ i- pueiiy i
-CH 2 CH 2 -
Z =
2-naphthalenyl
3,6-di^4e-2-pyndinyI
-CH=C(CH 3 )-
Z =
3-Me-nhenvl
4-Me-phenyl
-CH=C(CH 3 )-
Z =
3,5-diMe-phenyl
j-\--i-pnenyi
-CH=C(CH 3 )-
Z =
4-Cl-phenyl
j-w^r ^ -pnenyi
-CH=C(CH 3 )-
Z =
4-OCFo -nhenvl
O i""T ~U I
3-<_r3-pnenyl
-CH=C(CH 3 )-
Z =
4-CF">-T*he*nvl
z-napntnalenyl
-CH=C(CH 3 )-
z =
4-CFi-2-TwriHinv1
6-CF 3 -2-pyridinyl
-CH=N-N=C(CH 3 )-
Z =
4-Me-phenyl
-CH=N-N=C(CH 3 )-
Z =
3-CF-a -nhetivl
4-CF 3 -phenyl |
-CH=N-N=C(CH 3 )-
Z =
3-OCFo -nhenvl
4-ucr 3 -phenyl
-CH=N-N=C(CH*)-
z =
, j-uuvic-pncny i
3-Cl-phenyl
-CH=N-N=C(CH 3 )-
z =
■ Vfl lit/ 11 y 1
3,5-aiCl-phenyl
-CH=N-N=C(CH 3 )-
z =
4-1 ri — ^-TTvnH Hin\/1
« wi -i ^•jjjriiuixij'l
>-Cr 3-z-pynainyl
-CH=N-N=C(CH 3 )-
z =
6-CF"5-2-nvridiriv1
u -4 1 * ¥ f !*■ HI IV I
4-Me-2 -pyndinyl
-CH=N-N=C(CH 3 )-
z =
5 -Me-2-pyridinyl
6-Me-2-pyridinyl
-CH=N-N=C(CH 3 )-
z =
2 -naphthaleny 1
4, 6-diMe-2 -pyrid iny 1
-CH=N-N=C(CH 3 )-
z =
3 -Et-phenyl
t _ X3U
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
3 -Me-pheny 1
*T"ivie-pxicnyi
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
3 ,5-diMe-phenyl
0 v^i -pncny 1
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-Cl-phenyl
j , d -ai^i-pneny 1
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
3 -CF3 -phenyl
H-v^r 3 -pnenyi
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
3.5-dif CFi Vnhenvl
j-ULr 3-pHenyi
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-OCFa -nhenvl
-CH 2 0-N=C(CH 3 )C(=NOCH^)-
z =
f-Bu
z-napntnaienyi
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-/-Bu-phenyl
4-Me-2-pyridinyl
-CH 2 0-N^(CH 3 )C(=NOCH 3 )-
z =
5-Me-2-pyridinyl
6-Me-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-CF 3 -2-pyridinyl
5-CF 3 -2-pyridinyl
-CH 2 0-N-C(CH 3 )C(=NOCH 3 )-
z =
6-CF 3 -2-pyridinyl
4,6-diMe-2-pyridinyl
-CH 2 0-N=C(CH 3 )C(=NOCH 3 )-
z =
4-CF 3 -2-pyrimidinyl
6-CF 3 -2-pyrimidinyl
-CH=N-N(CH 3 )-
z =
3-Me-phenyl
4-Me-phenyl
-CH=N-N(CH 3 >-
z =
3,5-diMe-phenyl
3-Cl-phenyl
WO 99/28305
PCT/US98/24265
119
Y
Column 1
V^UIUZXIII A
-CH=N-N(CH 3 )-
Z =
4-Cl-phenyl
j,j-uici-pnenyi
-CH=N-N(CH 3 )-
Z =
3-CF 3 -phenyl
H-v.-r^-pnenyi
-CH=N-N(CH 3 )-
Z =
3-OCFo -nhenvl
^-<jur 3-pnenyi
-CH=N-N(CH 3 )-
z =
2-narjhthalenvl
*f- t-i5 u-pneny I
-CH=N-N(CH 3 )-
z =
4— f 1 — / _ 1 Til / 1
t iv±c-i-pyjiuiuyi
5-Me-2-pyndinyl
-CH=N-N(CH 3 )-
z =
u ivic-^-pyiiaiiiyi
4-CF 3 -2-pyridinyl
-CH=N-N(CH 3 )-
z =
— ' 3 ^ pyiiumyi
6-CF 3 -2-pyridinyl
-CH=N-N(CHo)-
z =
*t,G-uuvie-z-pyjiQinyi
4-CF 3 -2-pyrimidinyl
-CH 2 OC(SMe)=N-
z =
*t-^r 3 -pnenyi
3-CF 3 -phenyl
-CH 2 OC(SMe)=N-
z =
t- \j^r 3 -pncnyi
3-OCF 3 -phenyl
-CH 2 OC(SMe)=N-
z =
^-O-nhpnvl
•J v^i pncnyi
4-Cl-phenyl
-CH 2 OC(SMe)=N-
Z -
j>j uiv--j-piicnyi
3-Mc-phenyl
-CH?OC(SMe)=N-
z —
4-Me-phenyl
3,5-diMe-phenyl
-CH 2 OC(SMe)=N-
z =
z.-ii<tpnuiaicnyi
6-Me-2-pyridinyl
-CH 2 OC(SMe)=N-
z =
T-ivAc-x~pyrniinyi
4,6-diMe-2-pyndinyl
-CH 2 OC(SMe)=N-
z =
j-^j , 3 -^-pyriuiIjyi
5-Me-2-pyridinyl
-CH 2 OC(=S)NMe-
z =
4-f~ 1 F'» -Tlfrlf»TI\/l
~ "2 jjuciiyi
j-CF3-pnenyl
-CH 2 OC(=S)NMe-
z =
4-OCF 3 -phenyl
-> *wl r ^ -pneny i
-CH 2 OC(=S)NMe-
z =
3-Cl-phenyl
4-Cl-phenyl
-CH 2 OC(=S)NMe-
z =
3,5-diCl-phenyl
j -ivic-pncny i
-CH 2 OC(=S)NMe-
z =
4-Me-phenyl
3,5-diMe-phenyl
-CH 2 OC(=S)NMe-
z =
2-naphthalenyl
u-ivie-z -py nuiiiyi
-CH 2 OC(=S)NMe-
z =
4-Me-2-pyridinyl
**, o-uuvic-z -pynainy i
-CH 2 OC(=S)NMe-
z =
5-CF 3 -2-pyridinyl
5-Me-2 -pyridiny I
-SCH 2 -
z =
2-Me-phenyl
uuvic-piiciiyi
-SCH 2 -
z =
3-CF 3 -phenyl
4-CF 3 -phenyl
-SCH 2 -
z =
4-Me-Dhenvl
^ LJii n nam rl
*r-f-t3u-pnenyi
-SCH 2 -
z =
3-Cl-ohenvl
**-i_4-pnenyi
-SCH?-
z =
O-Mp- S-f^l -nil Pm/1
3-/-Bu-phenyl
-SCH 5 -
z =
ilapilLiUtlCIly 1
1 -naphthalenyl
-SCH 2 -
z =
3-pyridinyl
4-pyridinyl
-SCH 2 -
z =
6-Me-2-pyridinyl
5,6,7,8-tetrahydro-2-
naphthalenyl
-CH 2 0-N=C(SCH 3 )-
z =
3-CF 3 -phenyl
3-OCF 3 -phenyl
-CH 2 0-N=C(SCH 3 )-
z =
3-Me-phenyl
4-CF 3 -phenyl
-CH 2 0-N=C(SCH 3 )-
z =
4-OCF 3 -phenyl
4-Me-phenyl
-CH 2 0-N=C(SCH 3 )-
z =
3-Cl-phenyl
3,5-diCl-phenyl
WO 99/28305
PCT/US98/24265
120
Y
Column 1
column /.
-CH 2 0-N=C(cyclopropyl)- Z =
3-CF 3 -phenyl
3-OCF 3 -phenyl
-CH 2 0-N=C(cyclopropyl)- Z =
3-Me-phenyl
4-CF 3 -phenyl
-CH 2 0-N=C(cyclopropyl)- Z =
4-OCF 3 -phenyl
4-Me-phenyl
-CH 2 0-N=C(cyclopropyl> Z =
3-Cl-phenyl
3,5-diCl-phenyl
Table 6a
I — 1 , W — U, K.
- CH 3 , G - N, A = N, the floating double bond is attached to A, X = OCH3 and R 3 = CH 3
K
R?
r9
R?
3-Me-phenyl
4-Me-phenyl
3 -CF 3 -phenyl
4-CF 3 -phenyl
j-ULr 3-pnenyl
4-OCF3 -phenyl
3,5-di(CF 3 )-phenyl
3,5-diMe-phenyl
j-UL,rlr 2-pnenyl
4-OCHF 2 -phenyl 3-SCF 3 -phenyl
4-SCF 3 -phenyl
j-a^rtr 2-pnenyl
4-SCHF 2 -phenyl 3-Cl-phenyl
4-Cl-phenyl
3-Cl-4-Me-phenyl 3,4-diCI-phenyl
3-Br-phenyl
3-SMe-phenyl
4-SMe-phenyl
3-C=CH-phenyl
4-C=CH-phenyl
/-Bu
CF 3
3,5-diF-phenyl
3-cyclopropyl-phenyl
t — t1 w — 0 p2
- CH 3 , G = N, A = N, the floating double bond is attached to A, X = OCH 3 and R 3 = CI
IV
R?
R9
r£
^— K/f p .nhpn vl
4-Me-phenyl
3-CF 3 -phenyl
4-CF 3 -phenyl
3-OCF-) -nhenvl
4-OCF 3 -phenyl
3,5-di(CF 3 )-phenyl
3,5-diMe-phenyl
4-OCHF 2 -phenyl 3-SCF 3 -phenyl
4-SCF 3 -phenyl
4-SCHF 2 -phenyl
3-Cl-phenyl
4-Cl-phenyl
3 5-diCl-nhenvi
3-Cl-4-Me-phenyl 3,4-diCl-phenyl
3-Br-phenyl
3-SMe-nlienv'l
4-SMe-phenyl
3-CsCH-phenyl
4-C=CH-phenyl
<-Bu
CF 3
3,5-diF-phenyl
3-cyclopropyl-phenyl
T = T 1 , W = O, R 2 =
= CH 3 , G = N, A = N, the floating double bond is attached to A, X = OCH 3 and R 3 = CF 3
E?
3-Me-phenyl
4-Me-phenyl
3-CF 3 -phenyl
4-CF 3 -phenyl
3-OCF 3 -phenyl
4-OCF 3 -phenyl
3,5-di(CF 3 )-phenyl
3,5-diMe-phenyl
3-OCHF 2 -phenyl
4-OCHF 2 -phenyl
3-SCF 3 -phenyl
4-SCF 3 -phenyl
3-SCHF 2 -phenyl
4-SCHF 2 -phenyl
3-Cl-phenyl
4-Cl-phenyl
3,5-diCl-phenyl
3-Cl-4-Me-phenyl 3,4-diCl-phenyl
3-Br-phenyl
3-SMe-phenyl
4-SMe-phenyl
3-C=CH-phenyl
4-C=CH-phenyl
f-Bu
CF 3
3,5-diF-phenyl
3-cyclopropyl-phenyl
WO 99/28305
PCT/US98/24265
121
Table 6b
T = T 2 ,R 1 =CH 3 ,s;
3-Me-phenyl
3-OCF 3 -phenyI
3-OCHF 2 -phenyl
3-SCHF 2 -phenyl
3,5-diCl-phenyl
3-SMe-phenyl
t-Bu
T = T 2 ,R 1 =CH 3 , s =
3-Me-phenyl
3-OCF 3 -phenyl
3-OCHF 2 -phenyl
3-SCHF 2 -phenyl
3,5-diCl-phenyl
3-SMe-phenyl
f-Bu
■■ 1, R 5 = CH 3 and R 3 = CH 3
S£
4-Me-phenyl
4-OCF 3 -phenyl
4-OCHF 2 -phenyl
4-SCHF 2 -phenyl
3- Cl-4-Me-phenyl
4- SMe-phenyl
CF 3
l,R 5 = CH 3 andR 3 =Cl
R9
4-Me-phenyl
4-OCF 3 -phenyl
4-OCHF 2 -phenyl
4-SCHF 2 -phenyl
3- Cl-4-Me-phenyl
4- SMe-phenyl
CF 3
T = T 2 , Rl = CH 3> s = 1, R5 = C H 3 and R 3 = CF 3
3-Me-phenyl
3-OCF 3 -phenyl
3-OCHF 2 -phenyl
3-SCHF 2 -phenyl
3,5-diCl-phenyl
3-SMe-phenyl
t-Bu
R9
4-Me-phenyl
4-OCF 3 -phenyl
4-OCHF 2 -phenyl
4-SCHF 2 -phenyl
3- Cl-4-Me-phenyl
4- SMe-phenyl
CF 3
R9
3-CF 3 -phenyl
3,5-di(CF 3 )-phenyl
3-SCF 3 -phenyl
3-Cl-phenyl
3.4- diCl-phenyl
3-OCH-phenyl
3.5- diF-phenyl
R9
3-CF 3 -phenyl
3,5-di(CF 3 )-phenyl
3-SCF 3 -phenyl
3-Cl-phenyl
3.4- diCl-phenyl
3-CsCH-phenyl
3.5- diF-phenyl
R9
3-CF 3 -phenyl
3,5-di(CF 3 )-phenyl
3-SCF 3 -phenyl
3-Cl-phenyl
3.4- diCl-phenyl
3-OCH-phenyl
3.5- diF-phenyl
R?
4-CF 3 -phenyl
3,5-diMe-phenyl
4-SCF 3 -phenyl
4-Cl-phenyl
3- Br-phenyl
4- C=CH-phenyl
3-cyclopropyl-phenyl
R9
4-CF 3 -phenyl
3,5-diMe-phenyl
4-SCF 3 -phenyl
4-Cl-phenyl
3- Br-phenyl
4- C=CH-phenyl
3-cyclopropyl-phenyl
4-CF 3 -phenyl
3,5-diMe-phenyl
4-SCF 3 -phenyl
4-Cl-phenyl
3- Br-phenyl
4- C=CH-phenyl
3-cyclopropyl-phenyl
T = T 3 ,Rl=CH 3 , R5 =
3-Me-phenyl
3-OCF 3 -phenyl
3-OCHF 2 -phenyl
3-SCHF 2 -phenyl
i 3 and R 3 = CH 3
R9
4-Me-phenyl
4-OCF 3 -phenyl
4-OCHF 2 -phenyl
4-SCHF 2 -phenyl
Table 6c
R9
3-CF 3 -phenyl
3,5-di(CF 3 )-phenyl
3-SCF 3 -phenyl
3-Cl-phenyl
R9
4-CF 3 -phenyl
3,5-diMe-phenyl
4-SCF 3 -phenyl
4-Cl-phenyl
WO 99/28305
PCT7US98/24265
122
3,5-diCl-phenyl
3-SMe-phenyl
f-Bu
T = T 3 ,R 1 =CH 3 ,R 5 ;
3-Me-phenyl
3-OCF 3 -phenyl
3-OCHF 2 -phenyl
3-SCHF 2 -phenyl
3,5-diCl-phenyl
3-SMe-phenyl
t-Bu
3- Cl-4-Me-phenyl
4- SMe-phenyl
CF 3
: CH 3 and R 3 = CI
4-Me-phenyl
4-OCF 3 -phenyl
4-OCHF 2 -phenyl
4-SCHF 2 -phenyl
3- Cl-4-Me-phenyl
4- SMe-phenyl
CF 3
T = T 3 , Rl = CH 3 , R5 = CH 3 and R 3 = CF 3
R?
3-Me-phenyl
3-OCF 3 -phenyl
3-OCHF 2 -phenyl
3-SCHF 2 -phenyl
3,5-diCl-phenyl
3-SMe-phenyl
f-Bu
T = T 4 ,Rl=CH 3 , R6
R9
3-Me-phenyl
3-OCF 3 -phenyl
3-OCHF 2 -phenyl
3-SCHF 2 -phenyl
3,5-diCl-phenyl
3-SMe-phenyl
t-Bu
R9
4-Me-phenyl
4-OCF 3 -phenyl
4-OCHF 2 -phenyl
4-SCHF 2 -phenyl
3- Cl-4-Me-phenyl
4- SMe-phenyl
CF 3
R9
3.4- diCl-phenyl
3-C=CH-phenyl
3.5- diF-phenyl
R9
3-CF 3 -phenyl
3,5-di(CF 3 )-phenyl
3-SCF 3 -phenyl
3-Cl-phenyl
3.4- diCl-phenyl
3-CsCH-phenyl
3.5- diF-phenyl
r£
3-CF 3 -phenyl
3,5-di(CF 3 )-phenyl
3-SCF 3 -phenyI
3-Cl-phenyl
3.4- diCl-phenyl
3-C=CH-phenyl
3.5- diF-phenyl
Table 6d
= H, R 5 = CH 3 andR 3 = CH 3
R9
4-Me-phenyl
4-OCF 3 -phenyl
4-OCHF 2 -phenyl
4-SCHF 2 -phenyl
3- Cl-4-Me-phenyl
4- SMe-phenyl
CF 3
R9
3-CF 3 -phenyl
3,5-di(CF 3 )-phenyl
3-SCF 3 -phenyl
3-Cl-phenyl
3.4- diCl-phenyl
3-C3CH-phenyl
3.5- diF-phenyl
R9
3- Br-phenyl
4- C=CH-phenyl
3-cyclopropyl-phenyl
R9
4-CF 3 -phenyl
3,5-diMe-phenyl
4-SCF 3 -phenyl
4-Cl-phenyl
3- Br-phenyl
4- C^CH-phenyl
3-cyclopropyl-phenyl
r£
4-CF 3 -phenyl
3,5-diMe-phenyl
4-SCF 3 -phenyl
4-Cl-phenyl
3- Br-phenyl
4- OCH-phenyl
3-cyclopropyl-phenyl
r£
4-CF 3 -phenyl
3,5-diMe-phenyl
4-SCF 3 -phenyl
4-Cl-phenyl
3- Br-phenyl
4- CsCH-phenyl
3-cyclopropyl-phenyl
WO 99/28305
PCT7US98/24265
123
T = T 4 ,R 1 =CH 3 ,R 6
= H, R 5 = CH 3 and R 3
= C1
R?
R?
r£
3-Me-phenyl
4-Me-phenyl
3-CF 3 -phenyl
4-CF 3 -phenyl
3-OCF3 -phenyl
4-OCF 3 -phenyl
3,5-di(CF 3 )-phenyl
3,5-diMe-phenyl
j-ucrir 2 -pnenyl
4-OCHF 2 -phenyl
3-SCF 3 -phenyl
4-SCF 3 -phenyl
3-SCHF 2 -phenyl
4-SCHF 2 -phenyl
3-Cl-phenyl
4-Cl-Dhenvl
3,5-diCl-phenyl
3-Cl-4-Me-phenyl
3,4-diCl-phenyl
3-Br-phenyl
3-SMe-phenyl
4-SMe-phenyl
3-CsCH-phenyl
4-CsCH-phenyl
t-Bu
CF 3
3,5-diF-phenyl
3-cyclopropyl-phenyl
T = T 4 ,R 1 =CH 3 ,R 6
= H, R 5 = CH 3 and R 3
= CF 3
R9
R9
R9
R?
3-Me-phenyl
4-Me-phenyl
3 -CF 3 -phenyl
4-CF 3 -phenyl
3-OCF 3 -phenyl
4-OCF 3 -phenyl
3,5-di(CF 3 )-phenyl
3,5-diMe-phenyl
4-OCHF 2 -phenyl
3-SCF3 -phenyl
4-SCF 3 -phenyl
3-SCHF 2 -phenyl
4-SCHF 2 -phenyl
3-Cl-phenyl
4-Cl-phenyl
3,5-diCl-phenyl
3-Cl-4-Me-phenyl
3,4-diCl-phenyl
3-Br-phenyl
3-SMe-phenyl
4-SMe-phenyl
3-feCH-phenyl
4-C=CH-phenyl
/-Bu
CF 3
3,5-diF-phenyl
3-cyclopropyl-phenyl
Table 7a
T - T 1 , W - O, R 2 - CH 3 , G = N, A = N, the floating double bond is attached to A, X = OCH 3 and
No R 10 substituent (i.e.
• H)
s£
R?
R9
R9
3-Me-phenyl
4-Me-phenyl
3-CF 3 -phenyl
4-CF 3 -phenyl
3-OCF 3 -phenyl
4-OCF 3 -phenyl
3,5-di(CF 3 )-phenyl
3,5-diMe-phenyl
3-OCHF 2 -phenyl
4-OCHF 2 -phenyl
3-SCF 3 -phenyl
4-SCF 3 -phenyl
3-SCHF 2 -phenyl
4-SCHF 2 -phenyl
3-Cl-phenyl
4-Cl-phenyl
3,5-diCl-phenyl
3-Cl-4-Me-phenyl
3,4-diCl-phenyl
3-Br-phenyl
3-SMe-phenyl
4-SMe-phenyl
3-CsCH-phenyl
4-C=CH-phenyl
f-Bu
CF 3
3,5-diF-phenyl
3-cyclopropyl-phenyl
CH 3
I
Br
CI
CN
No R 9 substituent (i.e., H)
*
WO 99/28305
PCT/US98/24265
124
T = T 1 ,W = 0,R 2
3-Me-phenyl
3-OCF 3 -phenyl
3-OCHF 2 -phenyl
3-SCHF 2 -phenyl
3,5-diCl-phenyl
3-SMe-phenyl
r-Bu
CH 3
CN
T = T 1 ,W = 0, R 2 =
R 10 = CH 3
R9
3-Me-phenyl
3-OCF 3 -phenyl
3-OCHF 2 -phenyl
3-SCHF 2 -phenyl
3,5-diCl-phenyl
3-SMe-phenyl
/-Bu
CH 3
CN
= CH 3 , G - N, A = N, the floating double bond is attached to A, X = OCH 3 and R 10 = Br
4-Me-phenyl
4-OCF 3 -phenyl
4-OCHF 2 -phenyl
4-SCHF 2 -phenyl
3- Cl-4-Me-phenyl
4- SMe-phenyl
CF 3
I
No R 9 substituent (i.e., H)
R9
3-CF 3 -phenyl
3,5-di(CF 3 )-phenyl
3-SCF 3 -phenyl
3-Cl-phenyl
3.4- diCl-phenyl
3-CsCH-phenyl
3.5- diF-phenyl
Br
s2
4-CF 3 -phenyr
3,5-diMe-phenyl
4-SCF 3 -phenyl
4-Cl-phenyl
3- Br-phenyl
4- CsCH-phenyl
3-cyclopropyl-phenyl
CI
CH 3 , G - N, A = N, the floating double bond is attached to A, X = OCH 3 and
R9
4-Me-phenyl
4-OCF 3 -phenyl
4-OCHF 2 -phenyl
4-SCHF 2 -phenyl
3- Cl-4-Me-phenyl
4- SMe-phenyl
CF 3
I
No R 9 substituent (i.e., H)
R9
3-CF 3 -phenyl
3,5-di(CF 3 )-phenyl
3-SCF 3 -phenyl
3-Cl-phenyl
3.4- diCl-phenyl
3-C=CH-phenyl
3.5- diF-phenyl
Br
R?
4-CF 3 -phenyl
3,5-diMe-phenyl
4-SCF 3 -phenyl
4-Cl-phenyl
3- Br-phenyl
4- C=CH-phenyl
3-cyclopropyl-phenyl
CI
T = T 2 , R 1 = CH 3 , s ■■
S 9
3-Me-phenyl
3-OCF 3 -phenyl
3-OCHF 2 -phenyl
3-SCHF 2 -phenyl
3,5-diCl-phenyl
3-SMe-phenyl
/-Bu
CH 3
CN
Table 7b
: 1, R 5 = CH 3 and No R 10 substituent (i.e., H)
R 9
3-CF 3 -phenyl
EE
4-Me-phenyl
4-OCF 3 -phenyl
4-OCHF 2 -phenyl
4-SCHF 2 -phenyl
3- Cl-4-Me-phenyl
4- SMe-phenyl
CF3
I
No R 9 substituent (i.e., H)
3,5-di(CF 3 )-phenyl
3-SCF 3 -phenyl
3-Cl-phenyl
3.4- diCl-phenyl
3-CsCH-phenyl
3.5- diF-phenyl
Br
R 9
4-CF 3 -phenyl
3,5-diMe-phenyl
4-SCF 3 -phenyl
4-Cl-phenyl
3- Br-phenyl
4- CsCH-phenyl
3-cyclopropyl-phenyl
CI
WO 99/28305
PCT/US98/24265
125
T = T 2 , R 1 = CH 3 , s = 1, R5 = CH 3 and R 10 =
Br
R9
3-Me-phenyl
3-OCF 3 -phenyl
3-OCHF 2 -phenyl
3-SCHF 2 -phenyl
3,5-diCl-phenyl
3-SMe-phenyl
f-Bu
CH 3
CN
R 9
4-Me-phenyl
4-OCF 3 -phenyl
4-OCHF 2 -phenyl
4-SCHF 2 -phenyl
3- Cl-4-Me-phenyl
4- SMe-phenyl
CF 3
I
No R 9 substituent (i.e., H)
T = T 2 , R 1 = CH 3 , s = 1, R5 = CH 3 and R™ = CH 3
R 9
3-Me-phenyl
3-OCF 3 -phenyl
3-OCHF 2 -phenyl
3-SCHF 2 -pheny]
3,5-diCl-phenyl
3-SMe-phenyl
t-Bu
CH 3
CN
R9
4-Me-phenyl
4-OCF 3 -phenyl
4-OCHF 2 -phenyl
4-SCHF 2 -phenyl
3- Cl-4-Me-phenyl
4- SMe-phenyl
CF 3
I
NoR 9 substituent (i.e., H)
R 9
3-CF 3 -phenyl
3,5-di(CF 3 )-phenyl
3-SCF 3 -phenyl
3-Cl-phenyl
3.4- diCl-phenyl
3-C=CH-phenyl
3.5- diF-phenyl
Br
R9
3-CF 3 -phenyl
3,5-di(CF 3 )-phenyl
3-SCF 3 -phenyl
3-Cl-phenyl
3.4- diCl-phenyl
3-CsCH-phenyl
3.5- diF-phenyl
Br
R?
4-CF 3 -phenyi
3,5-diMe-phenyl
4-SCF 3 -phenyl
4-Cl-phenyl
3- Br-phenyl
4- C=CH-phenyl
3-cyclopropyl-phenyl
CI
R9
4-CF 3 -phenyl
3,5-diMe-phenyl
4-SCF 3 -phenyl
4-Cl-phenyl
3- Br-phenyl
4- C=CH-phenyl
3-cyclopropyl-phenyl
CI
T = T 3 ,r! =CH 3 ,R5;
R 9
3-Me-phenyl
3-OCF 3 -phenyl
3-OCHF 2 -phenyl
3-SCHF 2 -phenyl
3,5-diCl-phenyl
3-SMe-phenyl
t-Bu
CH 3
CN
Table 7c
: CH 3 and No R 10 substituent (i.e., H)
r£
4-Me-phenyl
4-OCF 3 -phenyl
4-OCHF 2 -phenyl
4-SCHF 2 -phenyl
3- Cl-4-Me-phenyl
4- SMe-phenyl
CF 3
I
No R 9 substituent (i.e., H)
3-CF 3 -phenyl
3,5-di(CF 3 >phenyl
3-SCF 3 -phenyl
3-Cl-phenyl
3.4- diCl-phenyl
3-C=CH-phenyl
3.5- diF-phenyl
Br
R 9
4-CF 3 -phenyl
3,5-diMe-phenyl
4-SCF 3 -phenyl
4-Cl-phenyl
3- Br-phenyl
4- C=CH-phenyl
3-cyclopropyl-phenyl
CI
WO 99/28305
PCT7US98/24265
126
T = T 3 ,R 1 =CH 3 , R 5
s£
3-Me-phenyl
3-OCF 3 -phenyl
3-OCHF 2 -phenyl
3-SCHF 2 -phenyl
3,5-diCl-phenyl
3-SMe-phenyl
/-Bu
CH 3
CN
= CH 3 andR^rzBr
R 9
4-Me-phenyl
4-OCF 3 -phenyI
4-OCHF 2 -phenyl
4-SCHF 2 -phenyl
3- Cl-4-Me-phenyl
4- SMe-phenyl
CF 3
I
No R 9 substituent (i.e., H)
T = T3, R 1 = CH 3> R5 = CH 3 and r'0 = C H 3
r£
3-Me-phenyl
3-OCF 3 -phenyl
3-OCHF 2 -phenyl
3-SCHF 2 -phenyl
3,5-diCl-phenyl
3-SMe-phenyl
f-Bu
CH 3
CN
R9
4-Me-phenyl
4-OCF 3 -phenyl
4-OCHF 2 -phenyl
4-SCHF 2 -phenyl
3- Cl-4-Me-phenyl
4- SMe-phenyl
CF 3
I
No R 9 substituent (i.e., H)
R 9
3-CF 3 -phenyl
3,5-di(CF 3 )-phenyl
3-SCF 3 -phenyl
3-Cl-phenyl
3.4- diCl-phenyl
3-C=CH-phenyl
3.5- diF-phenyl
Br
R?
3-CF 3 -phenyl
3,5-di(CF 3 )-phenyl
3-SCF 3 -phenyl
3-Cl-phenyl
3.4- diCl-phenyl
3-C=CH-phenyl
3.5- diF-phenyl
Br
R9
4-CF 3 -phenyr
3,5-diMe-phenyl
4-SCF 3 -phenyl
4-Cl-phenyl
3- Br-phenyl
4- CsCH-phenyl
3-cyclopropyl-phenyl
CI
R9
4-CF 3 -phenyl
3,5-diMe-phenyl
4-SCF 3 -phenyl
4-Cl-phenyl
3- Br-phenyl
4- C=CH-phenyl
3-cyclopropyl-phenyl
CI
T = t4r1 =CH 3 ,r5
R?
3-Me-phenyl
3-OCF 3 -phenyl
3-OCHF 2 -phenyl
3-SCHF 2 -phenyl
3,5-diCl-phenyl
3-SMe-phenyl
r-Bu
CH 3
CN
Table 7d
: CH 3> R 6 = H and No R 10 substituent (i.e., H)
R 9
R?
4-Me-phenyl
4-OCF 3 -phenyl
4-OCHF 2 -phenyl
4-SCHF 2 -phenyl
3- Cl-4-Me-phenyl
4- SMe-phenyl
CF 3
I
No R 9 substituent (i.e., H)
3-CF 3 -phenyl
3,5-di(CF 3 )-phenyl
3-SCF 3 -phenyl
3-Cl-phenyl
3.4- diCl-phenyl
3-CsCH-phenyl
3.5- diF-phenyl
Br
R9
4-CF 3 -phenyl
3,5-diMe-phenyl
4-SCF 3 -phenyl
4-Cl-phenyl
3- Br-phenyl
4- CsCH-phenyl
3-cyclopropyl-phenyl
CI
WO 99/28305
PCT7US98/24265
127
T = T« r1=cH 3 ,r5
R9
3-Me-phenyI
3-OCF 3 -phenyl
3-OCHF 2 -phenyl
3-SCHF 2 -phenyl
3,5-diCl-phenyl
3-SMe-phenyl
r-Bu
CH 3
CN
T = T 4 , Rl = CH 3> R5 =
R9
3-Me-phenyl
3-OCF 3 -phenyl
3-OCHF 2 -phenyl
3-SCHF 2 -phenyl
3,5-diCl-phenyl
3-SMe-phenyl
f-Bu
CH 3
CN
= CH 3 , R 6 =HandRlO = Br
R9
4-Me-phenyl
4-OCF 3 -phenyl
4-OCHF 2 -phenyl
4-SCHF 2 -phenyl
3- Cl-4-Me-phenyl
4- SMe-phenyl
CF 3
I
No R 9 substituent (i.e., H)
CH 3 , R6 = h and R 10 = CH 3
4-Me-phenyl
4-OCF 3 -phenyl
4-OCHF 2 -phenyI
4-SCHF 2 -phenyl
3- Cl-4-Me-phenyl
4- SMe-phenyl
CF 3
I
No R 9 substituent (i.e., H)
3-CF 3 -phenyl
3,5-di(CF 3 )-phenyl
3-SCF 3 -phenyl
3-Cl-phenyl
3.4- diCl-phenyl
3-CsCH-phenyl
3.5- diFrphenyl
Br
R 9
3-CF 3 -phenyl
3,5-di(CF 3 )-phenyl
3-SCF 3 -phenyl
3-Cl-phenyl
3.4- diCl-phenyl
3-C=CH-phenyl
3.5- diF-phenyl
Br
R 9
4-CF 3 -phenyl "
3,5-diMe-phenyl
4-SCF 3 -phenyl
4-Cl-phenyl
3- Br-phenyl
4- C=CH-phenyl
3-cyclopropyl-phenyl
CI
R?
4-CF 3 -phenyl
3,5-diMe-phenyl
4-SCF 3 -phenyl
4-Cl-phenyl
3- Br-phenyl
4- C=CH-phenyl
3-cyclopropyl-phenyl
CI
T = T 1 , W =
R 3 = CH 3
EH
NoR 12 (i.e.
2-Me
2-C1
2-F
2-OMe
2-Br
2-SMe
Table 8a
: O, G = N, A = N, the floating double bond is attached to A, R2 = CH 3 , X = OCH 3 and
,H)
rH
Ri 3
EH
lli
2-CN
2-F
4,6-diF
2-C1
6-Cl
NoR 13 (i.e., H)
2-F
3,5,6-triF
2-F
5-F
NoRl3 (i .e )H)
2-C1
4,6-diF
2-F
6-F
NoRl3(i. e .,H)
4-Br
2,6-diF
2-F
4-F
NoRl3 (i . e _ H)
4-1
2,6-diF
2-Et
NoR 13 (i.e.,H)
NoRl3( ix . iH)
2-F
3,6-diF
4-Me
2,6-diCl
NoR 13 (i.e.,H)
2-F
4,5-diF
4-Me
2,6-diF
WO 99/28305
PCT/US98/2426S
128
T - T 1 , W - O, G - N, A = N, the floating double bond is attached to A, R 2 = CH 3 , X = OCH 3 and R 3 = CI
Rl2
Rl3
fill
Ell
Ell
Ell
N0R 12 (i.e., H)
2-CN
2-C1
6-C1
2-Me
No R 13 (i.e., H)
2-F
3,5,6-triF
2-F
5-F
2-C1
N0R 13 (i.e.,H)
2-C1
4,6-diF
2-F
6-F
2-F
N0R 13 (i.e., H)
4-Br
2,6-diF
2-F
4-F
2-OMe
No R 13 (i.e., H)
4-1
2,6-diF
2-Et
NoR 13 (i.e.,H)
2-Br
N0R 13 (i.e., H)
2-F
3,6-diF
4-Me
2,6-diCl
2-SMe
N0R 13 (i.e.,H)
2-F
4,5-diF
4-Me
2,6-diF
T = T 1 , W = O, G
= N, A = N, the floal
ing double bond
is attached to A, R 2
= CH 3 ,X =
OCH3 and R 3 = CF 3
fill
Ri 3
Ell
Ell
Rl2
Ell
N0R 12 (i.e.,H)
2-CN
2-F
4,6-diF
2-C1
6-C1
2-Me
N0R 13 (i.e., H)
2-F
3,5,6-triF
2-F
5-F
2-C1
N0R 13 (i.e., H)
2-C1
4,6-diF
2-F
6-F
2-F
N0R 13 (i.e.,H)
4-Br
2,6-diF
2-F
4-F
2-OMe
N0R 13 (i.e.,H)
4-1
2,6-diF
2-Et
No R 13 (i.e., H)
2-Br
N0R 13 (i.e.,H)
2-F
3,6-diF
4-Me
2,6-diCl
2-SMe
N0R 13 (i.e.,H)
2-F
4,5-diF
4-Me
2,6-diF
Table 8b
T = T 2 , R 1 = CH 3 , s = 1, R 5 = CH 3 and R 3 = CH 3
Ri 2
Ell
EH
Ell
EH
Ell
No R 12 (i.e., H)
2-CN
2-F
4,6-diF
2-C1
6-C1
2-Me
No R 13 (i.e., H)
2-F
3,5,6-triF
2-F
5-F
2-C1
N0R 13 (i.e.,H)
2-C1
4,6-diF
2-F
6-F
2-F
N0R 13 (i.e., H)
4-Br
2,6-diF
2-F
4-F
2-OMe
N0R 13 (i.e., H)
4-1
2,6-diF
2-Et
N0R 13 (i.e.,H)
2-Br
N0R 13 (i.e.,H)
2-F
3,6-diF
4-Me
2,6-diCl
2-SMe
N0R 13 (i.e.,H)
2-F
4,5-diF
4-Me
2,6-diF
T = T 2 , R 1 = CH 3 ,
s = 1, R 5 = CH 3 an
d R 3 = CI
r12
Ell
EH
El!
Rl2
Ell
No R 1 2 (i.e., H)
2-CN
2-F
4,6-diF
2-C1
6-C1
2-Me
N0R 13 (i.e., H)
2-F
3,5,6-triF
2-F
5-F
2-C1
N0R 13 (i.e.,H)
2-C1
4,6-diF
2-F
6-F
2-F
N0R 13 (i.e., H)
4-Br
2,6-diF
2-F
4-F
WO 99/28305
PCT/US98/24265
129
Ell
Ell
Rl2
Ell
R 12
Rl 3
IN. _
2-OMe
No R 13 (i.e., H)
4-1
2,6-diF
2-Ft
Mrt P I 3 f \ a XX\
iNO Ix U.C, rl)
2-Br
NoR 13 (i.e.,H)
2-F
3,6-diF
4-Me
2 6-diCl
2-SMe
NoR 13 (i.e., H)
2-F
4,5-diF
4-Me
z,o-uir
T = T 2 , R 1 =CH 3>
s = 1, R5 = CH 3 an
dR 3 =
= CF 3
Ell
Ell
Ell
R 13
r13
NoR 12 (i,e.,H)
2-CN
2-F
4,6-diF
2-C1
6-C1
2-Me
NoR 13 (i.e.,H)
2-F
3,5,6-triF
2-F
5-F
2-C1
NoR 13 (i.e.,H)
2-C1
4,6-diF
2-F
6-F
2-F
NoR 13 (i.e.,H)
4-Br
2,6-diF
2-F
4-F
2-OMe
NoR 13 (i.e.,H)
4-1
2,6-diF
2-Et
NoR 13 (i.e.,H)
2-Br
No R* 3 (i.e., H)
2-F
3,6-diF
4-Me
2,6-diCl
2-SMe
NoR 13 (i.e., H)
2-F
4,5-diF
4-Me
2,6-diF
Table 8c
T = T 3 , Rl = CH 3 , R5 = CH 3 and R 3
= CH 3
Ell
Ell
Rl 2
Ell
Ell
Eil
No R 12 (i.e., H)
2-CN
2-F
4,6-diF
2-Cl
6-C1
2-Me
No R 13 (i.e., H)
2-F
3,5,6-triF
2-F
5-F
2-C1
No R 13 (i.e., H)
2-C1
4,6-diF
2-F
6-F
2-F
NoR 13 (i.e.,H)
4-Br
2,6-diF
2-F
4-F
2-OMe
NoR 13 (i.e.,H)
4-1
2,6-diF
2-Et
No R 1 3 (i.e., H
2-Br
No R 1 3 (i.e., H)
2-F
3,6-diF
4-Me
2,6-diCl
2-SMe
NoR 13 (i.e., H)
2-F
4,5-diF
4-Me
2,6-diF
T = T 3 , Rl = CH 3 , R5 = CH 3 and R 3 =
= C1
Rl2
Eil
Rl 2
Ell
Ell
Eil
No R 1 2 (i.e., H)
2-CN
2-F
4,6-diF
2-Cl
6-C1
2-Me
NoR 13 (i.e., H)
2-F
3,5,6-triF
2-F
5-F
2-C1
NoR 13 (i.e.,H)
2-C1
4,6-diF
2-F
6-F
2-F
No Rl 3 (i.e., H)
4-Br
2,6-diF
2-F
4-F
2-OMe
NoR 13 (i.e., H)
4-1
2,6-diF
2-Et
NoR 13 (i.e., H)
2-Br
No R 13 (i.e., H)
2-F
3,6-diF
4-Me
2,6-diCl
2-SMe
No R 13 (i. e ., H)
2-F
4,5-diF
4-Me
2,6-diF
WO 99/28305
PCT/US98/24265
T = T 3 ,R 1
= CH 3 , R 5 = CH 3 and R 3 =
= CF 3
Ell
Ril
No R 12 (i.e., H) 2-CN
2-F
2-Me
No R 1 3 (i.e., H)
2-F
2-C1
NoR 13 (i.e.,H)
2-C1
2-F
NoR 13 (i.e.,H)
4-Br
2-OMe
No R 13 (i.e., H)
4-1
2-Br
NoR 13 (i.e.,H)
2-F
2-SMe
NoR 13 (i.e., H)
2-F
Ell
Rl2
Ell
4,6-diF
2-C1
6-C1 -
3,5,6-triF
2-F
5-F
4,6-diF
2-F
6-F
2,6-diF
2-F
4-F
2,6-diF
2-Et
NoR 13 (i.e.,H)
3,6-diF
4-Me
2,6-diCl
4,5-diF
4-Me
2,6-diF
Table 8d
T = T4, Rl = CH 3 , R5 = CH 3 , R* = H and R 3 = CH 3
Rl2
Ri 3
Ell
R 1J
Ell
NoR 12 (i.e
-,H)
2-CN
2-F
4,6-diF
2-C1
6-Cl
2-Me
NoR 13 (i.e.,H)
2-F
3,5,6-triF
2-F
5-F
2-C1
NoR 13 (i.e.,H)
2-C1
4,6-diF
2-F
6-F
2-F
No R 13 (i.e., H)
4-Br
2,6-diF
2-F
4-F
2-OMe
NoR 13 (i.e., H)
4-1
2,6-diF
2-Et
No R 13 (i.e., H
2-Br
NoR 13 (i.e., H)
2-F
3,6-diF
4-Me
2,6-diCl
2-SMe
NoR 13 (i.e.,H)
2-F
4,5-diF
4-Me
2,6-diF
T = T 4 ,R 1
= CH 3 , R5 = CH 3 , R 6 = H and R 3 = CI
Ri 2
Ell
Ell
Ell
Ell
Ell
No R 12 (i.e., H)
2-CN
2-F
4,6-diF
2-C1
6-Cl
2-Me
NoR 13 (i.e.,H)
2-F
3,5,6-triF
2-F
5-F
2-C1
NoR 13 (i.e.,H)
2-C1
4,6-diF
2-F
6-F
2-F
NoR 13 (i.e.,H)
4-Br
2,6-diF
2-F
4-F
2-OMe
No R 13 (i.e., H)
4-1
2,6-diF
2-Et
NoR 13 (i.e.,H)
2-Br
N0RI 3 (i.e.,H)
2-F
3,6-diF
4-Me
2,6-diCl
2-SMe
No R 13 (i.e., H)
2-F
4,5-diF
4-Me
2,6-diF
T = T 4 ,R 1
= CH 3 ,r5 = cH 3 ,r6 = H
and R 3 = CF 3
Ri 2
Ri 3
Ell
Ell
Ell
Ell
NoR 12 (i.e
,H)
2-CN
2-F
4,6-diF
2-C1
6-Cl
2-Me
No R 13 (i.e., H)
2-F
3,5,6-triF
2-F
5-F
2-C1
NoR 13 (i.e., H)
2-C1
4,6-diF
2-F
6-F
2-F
NoR 13 (i.e., H)
4-Br
2,6-diF
2-F
4-F
WO 99/28305
PCTAJS98/24265
131
Rl3
Ri 2
Ri 3
Ri 2
rI3
2-OMe
NoR 13 (i.e., H)
4-1
2,6-diF
1NO K*-' (i.e., ri)
2-Br
NoR 13 (i.e.,H)
2-F
3,6-diF
4-Me
2,6-diCl
2-SMe
NoR 13 (i.e., H)
2-F
4,5-diF
4-Me
2,6-diF
Table 9a
J = T l , W = 0,G
- N, A = N, the floating double bond is attached to A, R 2
— <~fl 3 , A
— wcri3 ana
R 3 = CH 3
Ri 3
Ell
Ell
r12
NoR 12 (i.e.,H)
2-CN
2-F
4,6-diF
2-C1
6-C1
2-Me
NoR 13 (i.e.,H)
2-F
3,5,6-triF
2-F
5-F
2-C1
No R 13 (i.e., H)
2-C1
4,6-diF
2-F
6-F
2-F
NoR 13 (i.e.,H)
4-Br
2,6-diF
2-F
4-F
2-OMe
NoR 13 (i.e.,H)
4-1
2,6-diF
2-Et
NoR 13 (i.e., H)
2-Br
NoR 13 (i.e.,H)
2-F
3,6-diF
4-Me
2,6-diCl
2-SMe
No R 13 (i.e., H)
2-F
4,5-diF i
4-Me
2,6-diF
T - T 1 , W - O, G - N, A = N, the floating double bond is attached to A, R 2 = CH 3 , X = OCH 3 and R 3 = CI
Rl2
EH
Ri 3
Ri 3
NoR 12 (i.e.,H)
2-CN
2-F
4,6-diF
2-C1
6-C1
2-Me
NoR 13 (i.e.,H)
2-F
3,5,6-triF
2-F
5-F
2-C1
NoR 13 (i.e.,H)
2-C1
4,6-diF
2-F
6-F
2-F
NoR 13 (i.e.,H)
4-Br
2,6-diF
2-F
4-F
2-OMe
NoR 13 (i.e.,H)
4-1
2,6-diF
2-Et
NoR 13 (i.e.,H)
2-Br
No R 13 (i.e., H)
2-F
3,6-diF
4-Me
2,6-diCl
2-SMe
No R 13 (i.e., H)
2-F
4,5-diF
4-Me
2,6-diF
T - T 1 , W - O, G = N, A = N, the floating double bond is attached to A, R 2 =
Ell
NoR 12 (i.e.,H)
2-Me
2-C1
2-F
2-OMe
2-Br
2-SMe
Ri!
2-CN
NoR 13 (:
NoR 13 (
NoR 13 (;
NoR 13 (;
No R 13 (
NoR 13 (;
■e., H)
•e-,H)
■e-, H)
•e.,H)
■e.,H)
■e., H)
Rl 2
2-F
2-F
2-C1
4-Br
4-1
2-F
2-F
Ell
4,6-diF
3,5,6-triF
4,6-diF
2,6-diF
2,6-diF
3,6-diF
4,5-diF
CH 3 , X = OCH3 and R 3 = CF 3
Ell Ell
2-C1 6-C1
2-F 5-F
2-F 6-F
2-F 4-F
2-Et NoR 13 (i.e., H)
4-Me 2,6-diCl
4-Me 2,6-diF
WO 99/28305
PCT/US98/24265
132
Table 9b
T = T 2 , r1 = CH 3> s = 1, R5 = CH 3 and R 3 = CH 3
Rl2
Rl2
R 13
No R 12 (i.e., H)
2-CN
2-F
2-Me
NoR 13 (i.e., H)
2-F
2-C1
No R 1 3 (i.e., H)
2-C1
2-F
No R 1 3 (i.e., H)
4-Br
2-OMe
No R^ (i. e .,H)
4-1
2-Br
NoR 13 (i.e.,H)
2-F
2-SMe
NoR 13 (i.e.,H)
2-F
T = T2,Rl =CH 3 ,
s = l,R 5 = CH 3 andR 3 =
Rl2
Rl3
No R 1 2 (i.e., H)
2-CN
2-F
2-Me
NoR 13 (i.e.,H)
2-F
2-C1
NoR 13 (i. e .,H)
2-C1
2-F
NoR 13 (i.e.,H)
4-Br
2-OMe
NoR 13 (i.e., H)
4-1
2-Br
NoR 13 (i.e.,H)
2-F
2-SMe
N0RI 3 (i.e.,H) |
2-F
Rl2
T = T 2 , Rl =CH 3 ,
s = 1, RS = CH 3 and R 3 =
= CF 3
si 2 .
si 3 .
Rl 2
No R 12 (i.e., H)
2-CN
2-F
2-Me
No R 13 (i.e., H)
2-F
2-C1
NoR 13 (i.e., H)
2-C1
2-F
NoR 13 (i.e.,H)
4-Br
2-OMe
NoR 13 (i.e.,H)
4-1
2-Br
NoR 13 (i.e.,H)
2-F
2-SMe
NoR 13 (i.e.,H)
2-F
Rl2
Ri 3
4,6-diF
2-C1
6-C1
3,5,6-triF
2-F
5-F
4,6-diF
2-F
6-F
2,6-diF
2-F
4-F
2,6-diF
2-Et
NoR 13 (i.e.,t
3,6-diF
4-Me
2,6-diCl
4,5-diF
4-Me
2,6-diF
Eil
Bi 2 .
EH
4,6-diF
2-C1
6-C1
3,5,6-triF
2-F
5-F
4,6-diF
2-F
6-F
2,6-diF
2-F
4-F
2,6-diF
2-Et
NoR 13 (i.e., H)
3,6-diF
4-Me
2,6-diCl
4,5-diF
4-Me
2,6-diF
Ri 3
si 2
EH
4,6-diF
2-C1
6-C1
3,5,6-triF
2-F
5-F
4,6-diF
2-F
6-F
2,6-diF
2-F
4-F
2,6-diF
2-Et
No R 1 3 (i.e., H)
3,6-diF
4-Me
2,6-diCl
4,5-diF
4-Me
2,6-diF
T = T 3 Rl = CH 3 , R5 = CH 3 and R 3 = CH
Table 9c
rH
EH
rH
Ell
Ri 2 .
No R 12 (i.e., H)
2-CN
2-F
4,6-diF
2-C1
6-C1
2-Me
NoR 13 (i.e.,H)
2-F
3,5,6-triF
2-F
5-F
2-C1
NoR 13 (i.e., H)
2-C1
4,6-diF
2-F
6-F
2-F
No R^ 3 (i.e., H)
4-Br
2,6-diF
2-F
4-F
Rl 3
WO 99/28305
PCT/US98/24265
133
Ell
Ell
Ell
r13
Rl2
IS.
r!3
2-OMe
NoR 13 (i.e., H)
4-1
2,6-diF
2-Et
No R I 3 f i e H
2-Br
NoR 13 (i.e.,H)
2-F
3,6-diF
4-Me
2 6-diC1
2-SMe
NoR 13 (i.e.,H)
2-F
4,5-diF
^ 1V1C
z,o-oir
T = T 3 , R 1 = CH 3 , R5 = CH 3 and R 3 =
= CI
rH
Ell
R 12
Rl 3
iv
NoR 12 (i.e.,H)
2-CN
2-F
4 7 6-diF
2-C1
6-C1
2-Me
No R 13 (i.e., H)
2-F
3,5,6-triF
2-F
5-F
2-C1
No R 13 (i.e., H)
2-C1
4 6-diF
z-r
o-r
2-F
NoR 13 (i.e.,H)
4-Br
^,o-ulr
4-F
2-OMe
NoR 13 (i.e., H)
4-1
2,6-diF
INO K. lJ (i.e., H)
2-Br
NoR 13 (i.e.,H)
2-F
3,6-diF
4-Me
2-SMe
NoR 13 (i.e.,H)
2-F
4 S-rfiF
uir
•f- IV1C
T = T 3 , Rl = CH 3 , R 5 = CH 3 and R 3 =
: CFo
r12
Ell
R 12
Rl 3
wl2
R 1J
No R 12 (i.e., H)
2-CN
2-F
4,6-diF
2-C1
2-Me
NoR 13 (i.e., H)
2-F
3,5,6-triF
2-F
5-F
2-C1 -
NoR 13 (i.e.,H)
2-C1
4,6-diF
2-F
6-F
2-F
NoR 13 (i.e.,H)
4-Br
2,6-diF
2-F
4-F
2-OMe
NoR 13 (i.e., H)
4-1
2,6-diF
2-Et
NoR 13 (i.e., H)
2-Br
NoR 13 (i.e., H)
2-F
3,6-diF
4-Me
2,6-diCl
2-SMe
NoR 13 (i.e.,H)
2-F
4,5-diF
4-Me
2,6-diF
Table 9d
T = T 4 , R 1 = CH 3 , R5 = CH 3 , R6 = H and R 3 = CH 3
Ell
Ell
Rl 3
Rl2
Ell
NoR 12 (i.e.,H)
2-CN
2-F
4,6-diF
2-C1
6-C1
2-Me
NoR 13 (i.e.,H)
2-F
3,5,6-triF
2-F
5-F
2-C1
N0RI 3 (i.e.,H)
2-C1
4,6-diF
2-F
6-F
2-F
No R 13 (i.e., H)
4-Br
2,6-diF
2-F
4-F
2-OMe
NoR 13 (i.e.,H)
4-1
2,6-diF
2-Et
No R 13 (i.e., H)
2-Br
NoR 13 (i.e.,H)
2-F
3,6-diF
4-Me
2,6-diCl
2-SMe
NoR 13 (i.e.,H)
2-F
4,5-diF
4-Me
2,6-diF
WO 99/28305
PCT/US98/24265
134
T = T^, Rl = CH 3 , R5 = CH 3 , R6 = H and R3 = CI
RH
Rl2
Ell
M n R 12 /: p i_n
2-F
4,6-diF
2-Me
NoR^fi^H)
2-F
3,5,6-triF
2-C1
No R 13 (i.e., H)
2-C1
4,6-diF
2-F
No R 1 3 (i.e., H)
4-Br
2,6-diF
2-OMe
No R 1 3 (i.e., H)
4-1
2,6-diF
2-Br
No R 1 3 (i.e., H)
2-F
3,6-diF
2-SMe
NoR 13 (i.e., H)
2-F
4,5-diF
T = T4,Rl=CH3, R 5 = CH 3 ,R6 = HandR3=CF 3
Rl2
Ell
RH
Ell
No R 12 (i.e., H)
2-CN
2-F
4,6-diF
2-Me
No R 1 3 (i.e., H)
2-F
3,5,6-triF
2-C1
No R* 3 (i.e., H)
2-C1
4,6-diF
2-F
No R 13 (i.e., H)
4-Br
2,6-diF
2-OMe
No R 13 (i.e., H)
4-1
2,6-diF
2-Br
No R 13 (i.e., H)
2-F
3,6-diF
2-SMe
NoR 13 (i.e., H)
2-F
4,5-diF
Table 10
T = T 1 , W = O, G = N, A = N, the floating double bond is Y 1
attached to A, R 2 = CH 3 , X = OCH 3> R 3 = CH 3
T = T 1 , W = O, G = N, A = N, the floating double bond is Y 1
attached to A, R 2 = CH 3 , X = OCH 3 , R 3 = CH 3
T = T 1 , W = O, G = N, A = N, the floating double bond is Y 1
attached to A, R 2 = CH 3 , X = OCH 3 , R 3 = CH 3
T = T 1 , W = O, G = N, A = N, the floating double bond is Y 1
attached to A, R 2 = CH 3 , X = OCH 3 , R 3 = CH 3
T = T 1 , W = O, G = N, A = N, the floating double bond is Y 1
attached to A, R 2 = CH 3 , X = OCH 3 , R 3 = CI
T = T 1 , W = O, G = N, A = N, the floating double bond is Y 1
attached to A, R 2 = CH 3 , X = OCH 3 , R 3 = CI
T = T 1 , W = O, G = N, A = N, the floating double bond is Y 1
attached to A, R 2 = CH 3 , X = OCH 3 , R 3 = CI
T = T 1 , W = O, G = N, A = N, the floating double bond is Y 1
attached to A, R 2 = CH 3 , X = OCH 3 , R 3 = CI
Ri 2
Ell
2-C1
6-C1 '
2-F
5-F
2-F
6-F
2-F
4-F
2-Et
NoR 13 (i.e.,H)
4-Me
2,6-diCl
4-Me
2,6-diF
Ell
Ell
2-C1
6-C1
2-F
5-F
2-F
6-F
2-F
4-F
2-Et
No R * 3 (\ *. u\
4-Me
2,6-dici
4-Me
1 6-HiF
^-,u nit
Column 1
Column 2
OH
OSOtCHt
CHO
CH2CI
CH->Br
CHoI
CH2OH
OH
OS0 2 CH 3
CHO
CH 2 C1
CH 2 Br
CH 2 I
CH 2 OH
CH 2 OS0 2 CH 3
WO 99/28305
PCT/US98/24265
135
= T 1 , W = O, G = N, A = N, the floating double bond is
attached to A, R 2 = CH 3 , X = OCH 3 , R 3 = CF 3
= T 1 , W = O, G = N, A = N, the floating double bond is
attached to A, R 2 = CH 3 , X = OCH 3 , R 3 = CF 3
= T 1 , W = O, G = N, A = N, the floating double bond is
attached to A, R 2 = CH 3 , X = OCH 3 , R 3 = CF 3
= T 1 , W = O, G = N, A = N, the floating double bond is
attached to A, R 2 = CH 3 , X = OCH 3 , R 3 = CF 3
= T 2 , Rl = CH 3 , s = 1, R5 = CH 3 , R 3 = CH 3
= T 2 , R 1 = CH 3 , s = 1, RS = CH 3 , R 3 = CH 3
= T 2 , Rl = CH 3 , s = 1, R5 = CH 3 , R 3 = CH 3
= T 2 R 1 = CH 3 , s = 1, R5 = CH 3 , R 3 = CH 3
= T 2 , Rl = CH 3> s = 1, R5 = C H 3 , R 3 = CI
= T 2 Rl = CH 3 , s = 1, R5 = CH 3 , R 3 = CI
= T 2 Rl = CH 3 , s = 1, R 5 = CH 3 , R3 = CI
= T 2 Rl = CH 3 , s = 1, R5 = CH 3 , r3 = ci
= T 2 Rl = CH 3 , s = 1, R5 = CH 3 , r3 = CF 3
= T 2 Rl = CH 3 , s = 1, R5 = CH 3 , r3 = CF 3
T 2 Rl = CH 3> s = 1, R5 = CH 3 , R 3 = CF 3
T 2 , Rl = CH 3 , s = 1, R5 = CH 3> R 3 = CF 3
T 3 , Rl = CH 3 , R5 = CH 3 , R3 = CH 3
T 3 , Rl = CH 3 , R5 = CH 3 , R 3 = CH 3
T 3 , Rl = CH 3 , R5 = CH 3 , R3 = CH 3
T 3 , Rl = CH 3 , R5 = CH 3 , R3 = CH 3
T 3 , Rl = CH 3 , R5 = CH 3 , R 3 = ci
T 3 , Rl = CH 3 , R5 = CH 3 , R 3 = CI
T 3 , Rl = CH 3 , R5 = CH 3 , R 3 = CI
T 3 , Rl = CH 3 , R5 = CH 3 , R 3 = CI
T 3 , Rl = CH 3 , R5 = CH 3 , R 3 = CF 3
T 3 , Rl = CH 3 , R5 = CH 3 , R 3 = CF 3
T 3 , Rl = CH 3 , R5 = CH 3 , R 3 = CF 3
T3, Rl = CH 3 , R5 = CH 3 , R 3 = CF 3
T 4 , R 1 = CH 3 , R5 = CH 3> R6 = H, R3 = CH 3
T 4 , Rl = CH 3 , R5 = CH 3> R« = H, R 3 = CH 3
T 4 Rl = CH 3> R5 = CH 3 , R6 = H> R 3 = C H 3
T 4 Rl = CH 3 , R5 = CH 3> R6 = H, R 3 = CH 3
T 4 , Rl = CH 3 , R5 = CH 3 , R6 = H, r3 = CI
Column 1
Column 2
Y l =
OH
OS0 2 CH 3
yl =
v^rl2<~I
Y 1 =
yi =
yl =
x —
OH
Un
yl =
1 w
yl =
X12-DI
PU T
CH2I
Y l -
*-ji2*Jti
CH20S02CH 3
I —
0S02CH 3
pun
CH2CI
vl =
pi r t
C-H2I
Y l -
CH2OSO2CH3
yl =
z —
KJn
Uo\J2Uxl3
yl =
PHO
yi =
*-.xi2*
yl =
yi =
wow 2^-^13
yl =
CHO
v^ri2
yl =
CH2Br
v^x*2 A
yl =
CH2OH
\-.jn2»-/oi_/2*-'"^
yl =
OH
yi =
CHO
vnv
fu.pi
yi =
CH2Br
PU.T
i^n.21
yl =
PH-.OH
yi =
OH
L*3L/2Crl 3
yi =
run
Y i -
/~<T_T I
CH2I
yi =
CH 2 OH
CH 2 OS0 2 CH 3
Y» =
OH
OS0 2 CH 3
yi =
CHO
CH 2 C1
yi =
CH 2 Br
CH 2 I
yi =
CH 2 OH
CH 2 OS0 2 CH 3
yi =
OH
OS0 2 CH 3
WO 99/28305
PCT/US98/24265
136
10
15
Yl
Yl
Yl
Yl
Yl
Y l =
Yl:
Column 1
Column 2
CHO
CH 2 C1
CH 2 Br
CH 2 I
CH 2 OH
CH 2 OS0 2 CH 3
OH
OS0 2 CH 3
CHO
CH 2 C1
CH 2 Br
CH 2 I
CH 2 OH
CH 2 OSO?CH^
T 4 Rl = CH 3 , R5 = CH 3 , R 6 = H, R 3 = CI
T 4 R 1 = CH 3> R5 = CH 3 , R^ = H, R 3 = CI
T 4 Rl = CH 3 , R5 = CH 3 , R6 = H, R 3 = CI
T 4 Rl = CH 3 , R5 = CH 3 , R6 = H, R 3 = CF 3
T 4 , Rl = CH 3 , R 5 = CH 3> R 6 = H, R 3 = CF 3
T 4 , Rl = CH 3 , R5 = CH 3 , R 6 = H, R 3 = CF 3
T = T 4 , Rl = CH 3 , R5 = CH 3 , R<> = H, R 3 = CF 3
Formulation/Utility
Compounds of this . invention will generally be used as a formulation or composition
with an agriculturally suitable carrier comprising at least one of a liquid diluent, a solid
diluent or a surfactant. The formulation or composition ingredients are selected to be
consistent with the physical properties of the active ingredient, mode of application and
environmental factors such as soil type, moisture and temperature. Useful formulations
include liquids such as solutions (including emulsifiable concentrates), suspensions,
emulsions (including microemulsions and/or suspoemulsions) and the like which optionally
can be thickened into gels. Useful formulations further include solids such as dusts,
powders, granules, pellets, tablets, films, and the like which can be water-dispersible
("wettable") or water-soluble. Active ingredient can be (micro)encapsulated and further
formed into a suspension or solid formulation; alternatively the entire formulation of active
ingredient can be encapsulated (or "overcoated"). Encapsulation can control or delay release
of the active ingredient. Sprayable formulations can be extended in suitable media and used
at spray volumes from about one to several hundred liters per hectare. High-strength
compositions are primarily used as intermediates for further formulation.
The formulations will typically contain effective amounts of active ingredient, diluent
and surfactant within the following approximate ranges which add up to 100 percent by
weight.
Weight Percent
Active
Ingredient
Diluent
Surfactant
Water-Dispersible and Water-soluble
Granules, Tablets and Powders.
5-90
0-94
1-15
Suspensions, Emulsions, Solutions
(including Emulsifiable Concentrates)
5-50
40-95
0-15
Dusts
Granules and Pellets
1-25
0.01-99
70-99
5-99.99
0-5
0-15
High Strength Compositions
90-99
0-10
0-2
WO 99/28305
PCT/US98/24265
137
Typical solid diluents are described in Watkins, et al., Handbook of Insecticide Dust
Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid
diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York; 1950.
McCutcheon 's Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New
Jersey, as well as Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ.
Co., Inc., New York, 1964, list surfactants and recommended uses. All formulations can
contain minor amounts of additives to reduce foam, caking, corrosion, microbiological
growth and the like, or thickeners to increase viscosity.
Surfactants include, for example, polyethoxylated alcohols, polyethoxylated
alkylphenols, polyethoxylated sorbitan fatty acid esters, dialkyl sulfosuccinates, alkyl
sulfates, alkylbenzene sulfonates, organosilicones, MAT-dialkyltaurates, lignin sulfonates,
naphthalene sulfonate formaldehyde condensates, polycarboxylates, and
polyoxyethylene/polyoxypropylene block copolymers. Solid diluents include, for example,
clays such as bentonite, montmorillonite, attapulgite and kaolin, starch, sugar, silica, talc,
diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium
sulfate. Liquid diluents include, for example, water, W-dimethylformamide, dimethyl
sulfoxide, N-alkylpyrrolidone, ethylene glycol, polypropylene glycol, paraffins,
alkylbenzenes, alkylnaphthalenes, oils of olive, castor, linseed, tung, sesame, corn, peanut,
cotton-seed, soybean, rape-seed and coconut, fatty acid esters, ketones such as
cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, and alcohols
such as methanol, cyclohexanol, decanol and tetrahydrofurfuryl alcohol.
Solutions, including emulsifiable concentrates, can be prepared by simply mixing the
ingredients. Dusts and powders can be prepared by blending and, usually, grinding as in a
hammer mill or fluid-energy mill. Suspensions are usually prepared by wet-milling; see, for
example, U.S. 3,060,084. Granules and pellets can be prepared by spraying the active
material upon preformed granular carriers or by agglomeration techniques. See Browning,
"Agglomeration", Chemical Engineering, December 4, 1967, pp 147-48, Perry's Chemical
Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following,
and WO 91/13546. Pellets can be prepared as described in U.S. 4,172,714.
Water-dispersible and water-soluble granules can be prepared as taught in U.S. 4,144,050,
U.S. 3,920,442 andDE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S.
5,232,701 and U.S. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S.
3,299,566.
For further information regarding the art of formulation, see U.S. 3,235,361, Col. 6,
line 16 through Col. 7, line 19 and Examples 10-41; U.S. 3,309,192, Col. 5, line 43 through
Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167
and 169-182; U.S. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4;
Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961,
WO 99/28305
PCT/US98/24265
138
pp 81-96; and Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific
Publications, Oxford, 1989.
In the following Examples, all percentages are by weight and all formulations' are
prepared in conventional ways. Compound numbers refer to compounds in Index
Tables A-D.
Example A
Wettable Powder
Compound 3 65>0%
dodecylphenol polyethylene glycol ether 2.0%
sodium ligninsulfonate 4.0%
sodium silicoaluminate g 0%
montmorillonite (calcined) 23 0%
Example B
Granule
Compound 8 20 q O / 0
attapulgite granules (low volatile matter,
0.71/0.30 mm; U.S.S. No. 25-50 sieves) 90.0%.
Example C
Extruded Pellet
Compound 9 25 0%
anhydrous sodium sulfate 10.0%
crude calcium ligninsulfonate 5 0%
sodium alkylnaphthalenesulfonate 1.0%
calcium/magnesium bentonite 59 q%
Example D
Emulsifiable Concentrate
Compound 10 20 0%
blend of oil soluble sulfonates
and polyoxyethylene ethers 1 0.0%
isophorone 70 q%
The compounds of this invention are useful as plant disease control agents. The
present invention therefore further comprises a method for controlling plant diseases caused
by fungal plant pathogens comprising applying to the plant or portion thereof to be protected,
or to the plant seed or seedling to be protected, an effective amount of a compound of the
invention or a fungicidal composition containing said compound. The compounds and
compositions of this invention provide control of diseases caused by a broad spectrum of
fungal plant pathogens in the Basidiomycete, Ascomycete, Oomycete and Deuteromycete
classes. They are effective in controlling a broad spectrum of plant diseases, particularly
WO 99/28305
PCI7US98/24265
139
foliar pathogens of ornamental, vegetable, field, cereal, and fruit crops. These pathogens
include Plasmopara viticola, Phytophthora infestans, Peronospora tabacina,
Pseudoperonospora cubensis, Pythium aphanidermatum, Altemaria brassicae, Septoria
nodorum, Septoria tritici, Cercosporidium personatum, Cercospora arachidicola,
Pseudocercosporella herpotrichoides, Cercospora beticola, Botrytis cinerea, Monilinia
fructicola, Pyricularia oryzae, Podosphaera leucotricha, Venturia inaequalis, Erysiphe
graminis, Uncinula necatur, Puccinia recondita, Puccinia graminis, Hemileia vastatrix,
Puccinia striiformis, Puccinia arachidis, Rhizoctonia solani, Sphaerotheca fuliginea,
Fusarium oxysporum, Verticillium dahliae, Pythium aphanidermatum, Phytophthora
megasperma, Sclerotica sclerotiorum, Sclerotium rolfsii, Erysiphe poly goni, Pyrenophora
teres, Gaeumannomyces graminis, Rynchosporium secalis, Fusarium roseum, Bremia
lactucae and other generea and species closely related to these pathogens.
The compounds of this invention also exhibit activity against a wide spectrum of
foliar-feeding, fruit-feeding, stem or root feeding, seed-feeding, aquatic and soil-inhabiting
arthropods (term "arthropods" includes insects, mites and nematodes) which are pests of
growing and stored agronomic crops, forestry, greenhouse crops, ornamentals, nursery crops,
stored food and fiber products, livestock, household, and public and animal health. Those
skilled in the art will appreciate that not all compounds are equally effective against all
growth stages of all pests. Nevertheless, all of the compounds of this invention display
activity against pests that include: eggs, larvae and adults of the Order Lepidoptera; eggs,
foliar-feeding, fruit-feeding, root-feeding, seed-feeding larvae and adults of the Order
Coleoptera; eggs, immatures and adults of the Orders Hemiptera and Homoptera; eggs,
larvae, nymphs and adults of the Order Acari; eggs, immatures and adults of the Orders
Thysanoptera, Orthoptera and Dermaptera; eggs, immatures and adults of the Order Diptera;
and eggs, juveniles and adults of the Phylum Nematoda. The compounds of this invention '
are also active against pests of the Orders Hymenoptera, Isoptera, Siphonaptera, Blattaria,
Thysanura and Psocoptera; pests belonging to the Class Arachnida and Phylum
Platyhelminthes. Specifically, the compounds are active against southern com rootworm
(Diabrotica undecimpunctata howardi), aster leafhopper (Mascrosteles fascifrons), boll
weevil (Anthonomus grandis), two-spotted spider mite (Tetranychus urticae), fall armyworm
(Spodopterafrugiperda), black bean aphid (Aphis fabae), green peach aphid (Myzus
persica), cotton aphid (Aphis gossypii), Russian wheat aphid (Diuraphis noxia), English
gram aphid (Sitobion avenae), tobacco budworm (Heliothis virescens), rice water weevil
(Lissorhoptrus oryzophilus), rice leaf beetle (Oulema oryzae), whitebacked planthopper
(Sogatellajurcifera), green leafhopper (Nephotettix cincticeps), brown planthopper
(Nilaparvata lugens), small brown planthopper (Laodelphax striatellus), rice stem borer
(Chilo suppressalis), rice leafroller (Cnaphalocrocis medinalis), black rice stink bug
(Scotinophara lurida), rice stink bug (Oebalus pugnax), rice bug (Leptocorisa chinensis),
WO 99/28305
PCT/US98/24265
140
slender rice bug (Cletus puntiger), and southern green stink bug (Nezara viridula). The
compounds are active on mites, demonstrating ovicidal, larvicidal and chemosterilant
activity against such families as Tetranychidae including Tetranychus urticae, Tetranychus
cinnabarinus, Tetranychus mcdanieli, Tetranychus pacificus, Tetranychus turkestani,
5 Byrobia rubrioculus, Panonychus ulmi, Panonychus citri, Eotetranychus carpini borealis,
Eotetranychus, hicoriae, Eotetranychus sexmaculatus, Eotetranychus yumensis,
Eotetranychus banksi and Oligonychus pratensis; Tenuipalpidae including Brevipalpus
lewisi, Brevipalpus phoenicis, Brevipalpus californicus and Brevipalpus obovatus;
Eriophyidae including Phyllocoptruta oleivora, Eriophyes sheldoni, Aculus cornutus,
10 Epitrimerus pyri and Eriophyes mangiferae. See WO 90/10623 and WO 92/00673 for more
detailed pest descriptions.
Compounds of this invention can also be mixed with one or more other insecticides,
fungicides, nematocides, bactericides, acaricides, growth regulators, chemosterilants,
semiochemicals, repellents, attractants, pheromones, feeding stimulants or other biologically
1 5 active compounds to form a multi-component pesticide giving an even broader spectrum of
agricultural protection. Examples of such agricultural protectants with which compounds of
this invention can be formulated are: insecticides such as abamectin, acephate,
azinphos-methyl, bifenthrin, buprofezin, carbofuran, chlorfenapyr, chlorpyrifos,
chlorpyrifos-methyl, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin,
20 deltamethrin, diafenthiuron, diazinon, difiubenzuron, dimethoate, esfenvalerate, fenoxycarb,
fenpropathrin, fenvalerate, fipronil, flucythrinate, tau-fluvalinate, fonophos, imidacloprid,
isofenphos, malathion, metaldehyde, methamidophos, methidathion, methomyl, methoprene,
methoxychlor, methyl 7-chloro-2,5-dihydro-2-[[AT-(methoxycarbonyl)-A'-[4-
(trifluoromethoxy)phenyl]amino]carbonyl]indeno[l,2-e][l,3,4]oxadiazine-4a(3//)-
25 carboxylate (DPX-JW062), monocrotophos, oxamyl, parathion, parathion-methyl,
permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, rotenone,
sulprofos, tebufenozide, tefluthrin, terbufos, tetrachlorvinphos, thiodicarb, tralomethrin,
trichlorfon and triflumuron; fungicides such as azoxystrobin, benomyl, blasticidin-S,
Bordeaux mixture (tribasic copper sulfate), bromuconazole, captafol, captan, carbendazim,
30 chloroneb, chlorothalonil, copper oxychloride, copper salts, cymoxanil, cyproconazole,
cyprodinil (CGA 219417), diclomezine, dicloran, difenoconazole, dimethomorph,
diniconazole, diniconazole-M, dodine, edifenphos, epoxiconazole (BAS 480F), famoxadone,
fenarimol, fenbuconazole, fenpiclonil, fenpropidin, fenpropimorph, fluazinam,
fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fosetyl-aluminum, furalaxyl,
35 hexaconazole, ipconazole, iprobenfos, iprodione, isoprothiolane, kasugamycin,
kresoxim-methyl, mancozeb, maneb, mepronil, metalaxyl, metconazole, 5-methyl
7-benzothiazolecarbothioate (CGA 245704), myclobutanil, neo-asozin (ferric
methanearsonate), oxadixyl, penconazole, pencycuron, probenazole, prochloraz,
WO 99/28305
PCT/US98/24265
141
10
15
propiconazole, pyrifenox, pyroquilon, quinoxyfen, spiroxamine (KWG4168), sulfur,
tebuconazole, tetraconazole, thiabendazole, thiophanate-methyl, thiram, triadimefon,
triadimenol, tricyclazole, triticonazole, validamycin and vinclozolin; nematocides such as
aldoxycarb and fenamiphos; bactericides such as streptomycin; acaricides such as amitraz,
chinomethionat, chlorobenzilate, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin,
fenbutatin oxide, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and
tebufenpyrad; and biological agents such as Bacillus thuringiensis, Bacillus thuringiensis
delta endotoxin, baculovirus, and entomopathogenic bacteria, virus and fungi.
In certain instances, combinations with other fungicides or arthropodicides having a
similar spectrum of control but a different mode of action will be particularly advantageous
for resistance management.
Preferred for better control of plant diseases caused by fungal plant pathogens (e.g.,
lower use rate or broader spectrum of plant pathogens controlled) or resistance management
are mixtures of a compound of this invention with a fungicide selected from the group
cyproconazole, cyprodinil (CGA 219417), epoxiconazole, fenpropidin, fenpropimorph,
flusilazole and tebuconazole. Specifically preferred mixtures (compound numbers refer to
compounds in Index Tables A-D) are selected from the group: compound 8 and
cyproconazole; compound 8 and cyprodinil; compound 8 and epoxiconazole; compound 8
and fenpropidin; compound 8 and fenpropimorph; compound 8 and flusilazole; compound 8
20 and tebuconazole; compound 42 and cyproconazole; compound 42 and cyprodinil;
compound 42 and epoxiconazole; compound 42 and fenpropidin; compound 42 and
fenpropimorph; compound 42 and flusilazole; compound 42 and tebuconazole.
Plant disease control is ordinarily accomplished by applying an effective amount of a
compound of this invention either pre- or post-infection, to the portion of the plant to be
25 protected such as the roots, stems, foliage, fruit, seeds, tubers or bulbs, or to the media (soil
or sand) in which the plants to be protected are growing. The compounds can also be applied
to the seed to protect the seed and seedling.
For plant disease control, rates of application for these compounds can be influenced
by many factors of the environment and should be determined under actual use conditions.
30 Foliage can normally be protected when treated at a rate of from less than 1 g/ha to
5,000 g/ha of active ingredient. Seed and seedlings can normally be protected when seed is
treated at a rate of from 0.1 to 10 g per kilogram of seed.
Arthropod pests are controlled and protection of agronomic, horticultural and specialty
crops, animal and human health is achieved by applying one or more of the compounds of
35 this invention, in an effective amount, to the environment of the pests including the
agronomic and/or nonagronomic locus of infestation, to the area to be protected, or directly
on the pests to be controlled. Thus, the present invention further comprises a method for the
control of foliar and soil inhabiting arthropods and nematode pests and protection of
WO 99/28305
PCT/US98/24265
142
agronomic and/or nonagronomic crops, comprising applying one or more of the compounds
of the invention, or compositions containing at least one such compound, in an effective
amount, to the environment of the pests including the agronomic and/or nonagronomic locus
of infestation, to the area to be protected, or directly on the pests to be controlled. A
preferred method of application is by spraying. Alternatively, granular formulations of these
compounds can be applied to the plant foliage or the soil. Other methods of application
include direct and residual sprays, aerial sprays, seed coats, microencapsulations, systemic
uptake, baits, eartags, boluses, foggers, fumigants, aerosols, dusts and many others. The
compounds can be incorporated into baits that are consumed by the arthropods or in devices
such as traps and the like.
For the control of arthropod pests, the compounds of this invention can be applied in
their pure state, but most often application will be of a formulation comprising one or more
compounds with suitable carriers, diluents, and surfactants and possibly in combination with
a food depending on the contemplated end use. A preferred method of application involves
spraying a water dispersion or refined oil solution of the compounds. Combinations with
spray oils, spray oil concentrations, spreader stickers, adjuvants, other solvents, and
synergists such as piperonyl butoxide often enhance compound efficacy.
The rate of application required for effective control will depend on such factors as the
species of arthropod to be controlled, the pest's life cycle, life stage, its size, location, time of
year, host crop or animal, feeding behavior, mating behavior, ambient moisture, temperature,
and the like. Under normal circumstances, application rates of about 0.01 to 2 kg of active
ingredient per hectare are sufficient to control pests in agronomic ecosystems, but as little as
0.001 kg/hectare may be sufficient or as much as 8 kg hectare may be required. For
nonagronomic applications, effective use rates will range from about 1.0 to 50 mg/square
meter but as little as 0.1 mg/square meter may be sufficient or as much as 150 mg/square
meter may be required.
The following TESTS demonstrate the control efficacy of compounds of this invention
on specific pathogens. The pathogen pest control protection afforded by the compounds is
not limited, however, to these species. See Index Tables A-D for compound descriptions.
The following abbreviations are used in the Index Tables which follow: Ph = phenyl. The
abbreviation "Ex." stands for "Example" and is followed by a number indicating in which
example the compound is prepared.
WO 99/28305
PCT/US98/24265
143
INDEX TABLE A
See Index Table D for l H NMR data.
INDEX TABLE B
. Y.
CmDd No.
Y
Z
mo ( 0 0
1
-O-
3-(3,5-diCF 3 -Ph)-l,2,4-thiadiazol-5-yl
123-125
2
-O-
3-(3,5-diCl-Ph)- 1 ,2,4-thiadiazol-5-yl
68-72
3
-CH 2 0-N=C(CH 3 )-
3-CF 3 -Ph
78-80
4
-CH 2 0-
Ph
oil*
5
-CH 2 0-
CH 2 Ph
oil*
6
-CH 2 0-
CH 2 CH 2 Ph
oil*
14
-OCH 2 -
Ph
84-87
15
-OCH 2 CH 2 CH 2 -
Ph
98-100
16
-OCH 2 CH 2 -
Ph
oil*
17
-O-
6-(3-CF 3 -Ph)-3-pyridazinyl
218-221
18
-O-
6-(2-F-PhO)-4-pyrimidinyl
54-57
19
-O-
Ph
115-116
CmDd No. a
I
Rl
El
El
s
ya
Z
7 (Ex. 1,
Step D)
T 3
CH 3
CH 3
CH 3
-CH 2 0-N=C(CH 3 )-
3-CF 3 -Ph
8
9
j4
T 3
CH 3
CH 3
CH 3
CH 3
CH 3
CH 3
H -
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
3- CF 3 -Ph
4- CF 3 -2-
10 (Ex. 2,
Step C)
T 2
CH 3
CH 3
CH 3
1
-CH 2 0-N=C(CH 3 )-
pyridinyl
3-CF 3 -Ph
11
j4
CH 3
CH 3
CH 3
H -
-CH 2 0-N=C(CH 3 )-
4-CF 3 -2-
mp (°C)
oil*
oil*
oil*
oil*
pyridinyl
WO 99/28305
PCT/US98/24265
144
CmDd No. a
I Ri
R«
20
T 3 CHi
CHi
CHi
21
T 3 CHi
CHi
CH3
22
T 3 CH 3
CHi
CH 3
23
T 3 CHi
CH3
CH3
24
T 3 CH 3
CH3
CHi
25
T 3 CHi
CHi
CH3
26
T 3 CH3
CHi
v,n 3
27
T 3 CH3
CH3
«-«3
28
T 3 CHi
CHi
^ n 3
29
T 3 CHi
^"3
^ni
30
T 3 PH-.
v^rii
31
T 3 CHi
j v^j.±3
CH3
32
T 3 CH 3
, - rl 3
*-"3
33
T 3 CH3
CH3
V^Xjl
34
T 3 CHi
CI
TH,
35
T 3 CH 3
OCHi
Ln 3
36
T 3 CHi
3
F
^ n 3
37 b
T 3 CHi
F
CH->
v " "3
38
T 4 CHi
CH 3
CH3
x 1
39
T 4 CH3
CHi
CHi
H
1 1
40
T 4 CHi
CH3
CH 3
n
41
T 4 CHi
3
CH3
H
42
T 4 CHo
CHi
CH 3
H
n
43
T 4 CH1
CH3
44
T 4 CHi
CH3
H
45
T 4 CH 3
CI
CHi
v^i.13
H
46
T 4 CHi
wrl 3
1 1 T
n
47
T 4 CH 3
CH 3
CH 3
H
48
T 4 CH 3
OCH3
CH 3
H
49
T 4 CH 3
F
CH 3
H
50
T 4 CH 3
Br
CH 3
H
51
T 4 CH 3
I
CH 3
H
52
T 4 CH 3
CH 3
CH 3
H
d E isomers unless indicated otherwise.
b Z isomer at T 3 .
-CsC-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )C(=N-OCH 3 )-
-CH 2 0-N=C(CH 3 )C(=N-OCH 3 )-
-CH 2 ON=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )C(=N-OCH 3 )-
-CH 2 O-N=C(CH 3 )C(=N-0CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
, -CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 >
-CH 2 0-N=C(CH 3 >
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
-CH 2 0-N=C(CH 3 )-
mp (°C)
Ph .
78-82
3,5-diCl-Ph
108-110
3-Si(CH 3 ) 3
oil*
3-OCF 3 -Ph
oil*
3-F-Ph
oil*
3-Cl-Ph
oil*
3-Br-Ph
oil*
2-CHi-Ph
J
oil*
3-CH 3 -Ph
oil*
4-CHi-Ph
oil*
4-CFi-Ph
oil*
2-CFi-Ph
oil*
4-F-Ph
95-97
3-CF3-PI1
63-65
3-CF 3 -Ph
oil*
3-CF 3 -Ph
106-108
3-CFi-Ph
oil*
3-CF 3 -Ph
oil*
4-F-Ph
112-114
3-CF 3 -Ph
131-132
3,5-diCl-Ph
124-125
3-Si(CH 3 ) 3
oil*
3-OCF 3 -Ph
oil*
3-F-Ph
oil*
3-Cl-Ph
oil*
3-CH 3 -Ph
oil*
4-CH 3 -Ph
oil*
3-CF 3 -Ph
oil*
3-CF 3 -Ph
87-89
3-CF 3 -Ph
oil*
3-CF 3 -Ph
118-120
3-I-Ph
oil*
* See Index Table D for 'HNMR data.
WO 99/28305
PCT/US98/24265
145
INDEX TABLE C
Cmpd No. c
12 (Ex. 1,
Step C)
13 (Ex. 2,
Step B)
53
54
55
56
57
58
I
T 3
T 2
T 3
T 3
T 3
j4
T 4
CH3O
V
N— N
\
CH 3
59
CH3O
V
N— N
\
CH 3
c E isomer for T 2 , T 3 or T 4 unless indicated otherwise.
* See Index Table D for ! H NMR data.
INDEX TABLE D
Cmpd No. !h NMR Data (CDCl^ solution unless indicated otherwise) d
R
T
T
El
si
R5
R6
mo ("O
CH 3
CH 3
CH 3
CH 2 Br
oil*
CH 3
CH 3
CH 3
-
1 CH 2 Br
oil*
CI
Lri 2 Iir
CH 3
OCH3
CH 3
CH 2 Br
*
CH 3
F
CH 3
CH 2 Br
*
CH 3
Br
CH3
H
CH 2 Br
*
CH 3
I
CH 3
H
CH 2 Br
*
CH 3
OH
*
CH 3
CH 2 Br
*
4
5
6
7
8
9
8 2.22 (s, 3H), 3.46 (s, 3H), 3.93 (s, 3H), 5.05 (s, 2H), 6.95 (m, 3H), 7.30-7.50 (m, 4H),
7.40 (m, 1H)
5 2.21 (s, 3H), 3.45 (s, 3H), 3.93 (s, 3H), 4.55 (s, 2H), 4.56 (s, 2H), 7.20 (s, 1H),
7.25-7.30 (m, 7H)
6 2.19 <s, 3H), 2.92 (t, 2H, J=7.0), 3.46 (s, 3H), 3.69 (t, 2H, J=7.0), 3.93 (s, 3H), 4.51 (s,
2H), 7. 1 0-7.30 (m,8H)
5 2.19 (s, 3H), 2.27 (s, 3H), 3.86 (s, 3H), 4.04 (s, 3H), 5.23 (s, 2H), 7.15 (d, 1H,
J=1.7Hz), 7.25 (m, 1H), 7.37 (dd, 1H, J=1.7, 7.3Hz), 7.5 (m, 1H), 7.6 (d, 1H,
J=7.8Hz), 7.84 (m, 1H), 7.89 (d, 1H, J=0.5)
8 2.20 (s, 3H), 2.30 (s, 3H), 2.90 (d, 3H), 3.90 (s, 3H), 5.20 (s, 2H), 6.80 (br s, 1H),
7.20-7.40 (m, 6H), 7.80 (m, 2H)
8 2.19 (s, 3H), 2.36 (s, 3H), 3.87 (s, 3H), 4.04 (s, 3H), 5.28 (s, 2H), 7.17 (s, 1H), 7.25 (m,
1H), 7.40 (m, 1H), 7.45 (m, 1H), 8.15 (s, 1H), 8.74 (d, 1H, J=5.2)
WO 99/28305
PCT/US98/24265
13
16
22
23
24
146
Cmpd No. 1h NMR Data (CDCU solution unless indicated otherwise)* 1
10 5 2.19 (s, 3H), 2.26 (s, 3H), 3.69 (s, 3H), 3.80 (s, 3H), 5.22 (s, 2H), 7.17 (s, 1H), 7.25 (m,
1H), 7.5 (m, 1H), 7.6 (m, 2H), 7.8 (m, 1H), 7.91 (d, 1H, J=0.5)
12 5 3.9 (s, 3H), 4. l(s, 3H), 4.5 (s, 2H), 7.1-7.2 (m, 1H), 7.2-7.3 (m, 1H), 7.45(s, 1H)
8 3.7(s, 3H), 3.8 (s, 3H), 4.45 (s, 2H), 7.1 (s, 1H). 7.2-7.3 (m, 2H), 7.6 (s, 1H)
16 5 2.12 (s. 3H), 3.08 (t, 2H, J=7.1), 3.44 (s, 3H), 3.93 (s, 3H), 4.10-4.20 (m, 2H), 6.71 (s,
3H), 6.89 (m, 1H), 7.20-7.40 (m, 6H)
6 0.03 (s, 9H), 2.19 (s, 3H), 2.26 (s, 3H), 3.86 (s, 3H), 4.04 (s, 3H), 5.20 (s, 2H), 7.15 (s,
1H), 7.25-7.40 (m, 3H), 7.50-7.80 (m, 3H)
5 2.20 (s, 3H), 2.25 (s, 3H), 3.85 (s, 3H), 4.05 (s, 3H), 5.20 (s, 2H), 7. 15 (s, 1H), 7.20-
7.40 (m, 4H), 7.50 (s, 1H), 7.60 (m, 1H)
6 2.20 (s, 3H), 2.25 (s, 3H), 3.85 (s, 3H), 4.05 (s, 3H), 5.20 (s, 2H), 7.00 (m, 1H), 7.15 (s
1H), 7.20-7.40 (m, 5H)
25 5 2.20 (s, 3H), 2.25 (s, 3H), 3.85 (s, 3H), 5.04 (s, 3H), 5.20 (s, 2H), 7. 15 (s, 1H), 7.20-
7.40 (m, 4H), 7.50 (m, 1H), 7.60 (s, 1H)
26 5 2.19 (s, 3H), 2.22 (s, 3H), 3.86 (s, 3H), 4.04 (s, 3H), 5.21 (s, 2H), 7.15 (m, 1H), 7.20-
7.50 (m, 4H), 7.60 (m, 1H), 7.80 (m, 1H)
6 2.19 (s, 3H), 2.20 (s, 3H), 3.86 (s, 3H), 4.05 (s, 3H), 5.18 (s, 2H), 7.10-7.30 (m, 6H),
7.40 (m, 1H)
5 2.18 (a, 3H), 2.24 (s, 3H), 2.36 (s, 3H), 3.85 (s, 3H), 4.04 (s, 3H), 5.21 (s, 2H), 7.10-
7.50- (m, 7H)
6 2.19 (s, 3H), 2.23 (s, 3H), 2.35 (s, 3H), 3.86 (s, 3H), 4.04 (s, 3H), 5.20 (s, 2H), 7.15 (m,
1H), 7.20-7.50 (m, 4H)
6 2.19 (s, 3H), 2.26 (s, 3H), 3.86 (s, 3H), 4.04 (s, 3H), 5.23 (s, 2H), 7.16 (s, 1H), 7.26 (m,
1H), 7.36 (m, 1H), 7.60 (m, 2H), 7.80 (m, 2H)
31 6 2.20 (s, 3H), 2.21 (s, 3H), 3.87 (s, 3H), 4.05 (s, 3H), 5.19 (s, 2H), 7.10 (s, 1H), 7.20-
7.40 (m, 3H), 7.40-7.60 (m, 2H), 7.70 (m, 1H)
6 2.28 (s, 3H), 3.88 (s, 3H), 4.05 (s, 3H), 5.24 (s, 2H), 7.26 (s, 1H), 7.40-7.50 (m, 3H),
7.60 (m, 1H), 7.80 (m, 1H), 7.90 (m, 1H)
o 2.28 (s, 3H), 3.89 (s, 3H), 4.09 (s, 3H), 5.27 (s, 3H), 7.10 (m, 1H), 7.40-7.60 (m, 4H),
7.80 (s, 1H), 7.90 (s, 1H)
6 2.29 (s, 3H), 3.90 (s, 3H>, 4.05 (s, 3H), 5.22 (s, 2H), 7.00-7.10 (m, 1H), 7.40-7.60 (m,
3H), 7.80 (m, 1H), 7.90 (s, 1H)
5 0.03 (s, 9H), 2. 18 (s, 3H), 2.25 (s, 3H), 2.92 (d, 3H, J=4.8), 3.95 (s, 3H), 5.21 (s, 2H),
6.74 (br s, 1H), 7.14-7.50 (m, 5H), 7.60 (m, 1H), 7.80 (m, 1H)
5 2.18 (s, 3H), 2.23 (s, 3H), 2.93 (m, 3H), 3.90 (s, 3H), 5.21 (s, 2H), 6.80 (br s, 1H), 7.20
(m, 1H), 7.20-7.40 (m, 4H), 7.50 (s, 1H), 7.60 (m, 1H)
43 8 2.20 (s, 3H), 2.25 (s, 3H), 2.90 (m, 3H), 5.20 (s, 2H), 6.80 (m, 1H), 7.00 (m, 1H),
7.20-7.40 (m, 6H)
8 2.18 (s, 3H), 2.21 (s, 3H), 2.93 (m, 3H), 3.95 (s, 3H), 5.20 (s, 2H), 6.80 (m, 1H), 7.13
(m, 1H), 7.20-7.40 (m, 4H), 7.50 (m, 1H), 7.60 (m, 1H)
8 2. 18 (s, 3H), 2.23 (s, 3H), 2.37 (s, 3H), 2.92 (m, 3H), 3.95 (s, 3H), 5.21 (s, 2H), 6.72
(br s, 1H), 7.20-7.50 (m, 7H)
5 2.18 (s, 3H), 2.22 (s, 3H), 2.35 (s, 3H), 2.92 (m, 3H), 3.95 (s, 3H), 5.20 (s, 2H), 6.70
(brs, 1H), 7.10 (m, 3H), 7.20-7.30 (m, 2H), 7.50 (m, 2H)
27
28
29
30
34
36
37
41
42
44
46
47
WO 99/28305
PCT/US98/24265
147
Cmpd No. j H NMR Data (CDCh solution unless indicated otherwise)* 3
48 5 2.25 (s, 3H), 2.93 (m, 3H), 3.80 (s, 3H), 3.93 (s, 3H), 5.19 (s, 2H), 6.71 (br s, 1H), 6.94
(d, 1H, J=8.6), 7.30-7.50 (m, 4H), 7.50 (m, 1H), 7.80 (m, 1H), 7.90 (s, 1H)
50 8 2.27 (s, 3H), 2.96 (d, 3H, J=5.1), 3.96 (s, 3H), 5.21 (s, 2H), 6.80 (br s, 1H), 7.20 (m,
1H), 7.35 (m, 1H), 7.50 (m, 1H), 7.60 (m, 2H), 7.80 (m, 1H), 7.88 (s, 1H)
52 5 2.18 (s, 3H), 2.19 (s, 3H), 2.92 (s, 3H), 3.95 (s, 3H), 5.20 (s, 2H), 6.80 (br s, 1H), 7.00-
7.30 (m, 3H), 7.35 (m, 1H), 7.60 (m, 1H), 7.65 (m, 1H), 7.98 (m, 1H)
53 5 3.89 (m, 3H), 4.08 (s, 3H), 4.46 (s, 2H), 7.24 (m, 1H), 7.4 (m, 2H)
54 8 3.79 (s, 3H), 3.86 (s, 3H), 4.05 (s, 3H), 4.49 (s, 2H), 6.90 (d, J=8.4, 1H), 7.29 (d, J=2.3,
1H), 7.43 (dd, J=2.3 and 8.6, 1H)
55 8 3.90 (s, 3H), 4.10 (s, 3H), 4.48 (s, 2H), 7.00-7.10 (m, 1H), 7.35 (m, 1H), 7.40 (m, 1H)
56 8 3.89 (s, 3H), 4.08 (s, 3H), 4.44 (s, 2H), 7.19 (d, J=2.3, 1H), 7.3 (m, 1H), 7.50-7.70 (m
2H)
57 8 3.90 (s, 3H), 4.08 (s, 3H), 4.43 (s, 2H), 7. 13 (m, 2H), 7.80 (m, 1H)
58 S 2.05 (s, 3H), 3.49 (s, 3H), 3.92 (s, 3H), 6.53 (d, J=2.5, 1H), 6.60 (dd, J=2.5 and 8.5
1H), 7.01 (d, J=8.5, 1H)
59 8 2.20 (s, 3H), 3.45 (s, 3H), 3.95 (s, 3H), 4.45 (s, 2H), 7.20-7.40 (m, 3H)
H NMR data are in ppm downfield from tetramethylsilane. Coupling constants are indicated by J and
reported in Hertz. Couplings are designated by (s)-singlet, (d)-doublet, (t)-triplet, (m)-multiplet, dd-doublet
of doublets and (br s)-broad singlet.
BIOLOGTC AT . E XAMPLES OF THE INVENTION
Test compounds were first dissolved in acetone in an amount equal to 3% of the final
volume and then suspended at a concentration of 200 ppm in purified water containing
250 ppm of the surfactant Trem® 014 (polyhydric alcohol esters). The resulting test
suspensions were then used in Tests A-F. Spraying these 200 ppm test suspensions to the
point of run-off on the test plants is the equivalent of a rate of 500 g/ha.
TESTA
The test suspension was sprayed to the point of run-off on wheat seedlings. The
following day the seedlings were inoculated with a spore dust of Erysiphe graminis
f. sp. tritici, (the causal agent of wheat powdery mildew) and incubated in a growth chamber
at 20 °C for 7 days, after which disease ratings were made.
TESTB
The test suspension was sprayed to the point of run-off on wheat seedlings. The
following day the seedlings were inoculated with a spore suspension of Puccinia recondita
(the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20 °C for
24 h, and then moved to a growth chamber at 20 °C for 6 days, after which disease ratings
were made.
TEST C
The test suspension was sprayed to the point of run-off on rice seedlings. The
following day the seedlings were inoculated with a spore suspension of Pyricularia oryzae
WO 99/28305
PCT/US98/24265
10
148
(the causal agent of rice blast) and incubated in a saturated atmosphere at 27 °C for 24 h, and
then moved to a growth chamber at 30°C for 5 days, after which disease ratings were made.
TEST D
The test suspension was sprayed to the point of run-off on tomato seedlings. The
following day the seedlings were inoculated with a spore suspension of Phytophthora
infestans (the causal agent of potato and tomato late blight) and incubated in a saturated
atmosphere at 20 °C for 24 h, and then moved to a growth chamber at 20 °C for 5 days, after
which disease ratings were made.
TESTE
The test suspension was sprayed to the point of run-off on grape seedlings. The
following day the seedlings were inoculated with a spore suspension of Plasmopara viticola
(the causal agent of grape downy mildew) and incubated in a saturated atmosphere at 20 °C
for 24 h, moved to a growth chamber at 20 °C for 6 days, and then incubated in a saturated
atmosphere at 20 °C for 24 h, after which disease ratings were made.
15 TESTF
The test suspension was sprayed to the point of run-off on cucumber seedlings. The
following day the seedlings were inoculated with a spore suspension of Botrytxs cinerea (the
causal agent of gray mold on many crops) and incubated in a saturated atmosphere at 20 °C
for 48 h, and moved to a growth chamber at 20 °C for 5 days, after which disease ratings
20 were made.
Results for Tests A-F are given in Table A. In the table, a rating of 100 indicates 1 00%
disease control and a rating of 0 indicates no disease control (relative to the controls). A
dash (-) indicates no test results. ND indicates disease control not determined due to
phytotoxicity. # indicates significant activity.
Table A
Cmtxi No.
Test A
TestB
TestC
TestD
TestE
TestF
1
98#
0
0
0
0
2
83
85#
32
100#
23*
70#
3
100#
100#
100#
47
20*
95#
4
98#
99#
86#
100#**
7*
5
87#
100#
53
26
19*
0
6
87#
94#
0
47
33*
0
7
100#
97#
97#
0
49
8
97#
99#
74
35
31*
45
9
99#
100#
97#
26
14*
49
10
100#
99#
91#
0
13*
0
11
95#
100#
53
26
0
14
90#
27
0
0
40*
0
15
83#
85#
53
77#
13*
0
16
99#
99#
91#
0
6*
0
17
92#
0
0
20*
0
WO 99/28305
PCT/US98/24265
149
Cmpd No.
Test A
TestB
TestC
TestD
TestE
TestF
1 o
95#
0
0
100#
7*
0
1 o
90#
97#
0
0
13*
0
2V
97#
28
0
85#
29*
0
21
98#
0
74
43
24*
98#
22
99#
67#
53
92#
55#*
83
25
100#
97#
91#
0
17*
83
24
97#
0
91#
85#
30*
0
25
98#
27
91#
85#
37*
0
26
94#
27
74
45
76#*
98#
27
99#
27
0
45
18*
94
28
98#
27
53
23
34*
0
29
94#
85#
53
23
26*
0
30
99#
97#
53
0
40*
0
31
100#
99#
53
44
7*
43
32
100#
86#
0
92#
90#*
0
33
100#
85#
74
43
0*
0
34
96#
0
0
0
15*
45
35
90#
27
0
0
9*
99#
3o
95#
86#
0
0
29*
7
37
95#
0
0
0
-
0
3©
99#
100#
53
75#
16*
43
so
3y
98#
0
53
20
5*
0
4U
99#
97#
53
61
82#*
94
A 1
98#
100#
0
20
24*
98#
4z
99#
100#
94#
92#
24*
48
43
97#
100#
86#
92#
17*
83
AA
44
99#
100#
100#
75#
28*
98#
1U0#
0
0
23
14*
94
46
99#
100#
53
23
20*
99#
47
99#
100#
53
23
50#*
98#
48
96#
0
0
0
4*
99#
49
99#
99#
0
0
5*
82
50
97#
28
0
0
5*
7
51
95#
0
0
0
5*
7
52
95#
100#
74
63
29*
7
* Tested at lOppm.
20% plant injury also noted.
WO 99/28305
PCT/US98/24265
150
CLAIMS
What is claimed is:
1 . A compound selected from Formula I, TV-oxides and agriculturally suitable salts
thereof,
wherein:
Tis
T l
COOR 5
T2
COOR 5
RlO\
CONr6r 5
10
15
20
T 3 or T4 .
X is ORl, S(0) m Ri or halogen;
A is O, S, N, NR 5 or CR 7 ;
G is C or N; provided that when G is C, A is O, S or NR 5 and the floating double bond
is attached to G; and when G is N, A is N or CR 7 and the floating double bond is
attached to A;
W is O or S;
YZ is a group consisting of (a) 3 or more atoms independently selected from the group
C, N, O, S, Si and Ge, provided that at least 2 of said atoms are C, and
(b) additional atoms selected from H, F, CI, Br and I;
R 1 is C r C 6 alkyl, C r C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl,
C 2 -C 6 haloalkynyl, C 3 -C 6 cycloalkyl, C 2 -C 4 alkylcarbonyl or C 2 -C 4
alkoxycarbonyl ;
R 2 , R 5 and R* are each independently selected from the group H, C r C 6 alkyl, C r C 6
haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl,
c 3" c 6 cycloalkyl, C 2 -C 4 alkylcarbonyl and C 2 -C 4 alkoxycarbonyl;
WO 99/28305
PCT/US98/24265
151
R 3 is halogen, CF 3 , C,-C 3 alkyl or C r C 3 alkoxy;
R 4 is H, halogen, CF 3 , C r C 3 alkyl or C r C 3 alkoxy;
R 7 is H, halogen or methyl;
m is 0, 1 or 2; and
s is 0 or 1 ;
provided that
(a) when T is Tl, G is N, A is N, X is S(0) m Ri and m is 0; then the combination of Y
and Z is other than alkyl, haloalkyl or alkoxy;
(b) when T is T 1 , G is C and A is NR 5 ; then the combination of Y and Z is other than
alkyl or alkoxy; and
(c) when T is T 1 and R 3 is halogen, then R 4 is hydrogen.
2. A compound of Claim 1 wherein
Y is -O-, -(CH 2 ) r O-, -0(CH 2 ) r -, -CHR"0-N=C(R8)-, a direct bond, -(CH 2 ) r ,
-C(R11)=C(RH)-, -(CH 2 ) r S(0) m -, -C(R8) =N-0-CHR"-,
-CHR»SC(R8)=N-, -C(Ril)=N-N=C(RH)-, -CHR"0-N=C(R8)CH 2 S-,
-CHRHO-N=C(R8)CH 2 0-, -C(Rl 1)=N-N(CH 3 )-, -CHRH 0 C(R8)=N-, '
-CHRl !OC(=S)NRl 1-, -CHRl 1SC(=S)NRH., -S(CHRl l) r -, or
-CHRl lO-N=C(Ri i)C(=N-ORH). ; and the directionality of the Y
linkage is defined such that the moiety depicted on the left side of the
linkage is bonded to the phenyl ring having the R 3 and R 4 substituents
and the moiety on the right side of the linkage is bonded to Z;
Z is selected from
i) Cj-Cjo alkyl, Cj-Cjo haloalkyl or phenyl each optionally substituted
with R 9 and optionally substituted with one or more R 10 ;
ii) a ring selected from 5 or 6-membered aromatic heterocyclic ring,
each heterocyclic ring containing 1 to 4 heteroatoms independently
selected from the group nitrogen, oxygen, and sulfur, provided that each
heterocyclic ring contains no more than 3 nitrogens, no more than 1
oxygen, and no more than 1 sulfur, each aromatic heterocyclic ring
optionally substituted with R 9 and optionally substituted with one or
more R 10 ;
iii) a naphthalene ring optionally substituted with R 9 and optionally
substituted with one or more R 10 ; and
iv) a tetrahydronaphthalene ring optionally substituted with R 9 and
optionally substituted with one or more R 10 ;
R8 is H, C r C 3 alkyl, G r C 3 alkoxy, C r C 3 alkylthio, C r C 3 haloalkyl, C 2 -C 3
alkenyl, C 2 -C 3 alkynyl, cyclopropyl, cyano or NH 2 ;
WO 99/28305
PCT/US98/24265
15
152
R 9 is halogen; C r C 6 alkyl; C r C 6 haloalkyl; C r C 6 alkoxy;
C r C 6 haloalkoxy; C 2 -C 6 alkenyl; C 2 -C 6 haloalkenyl; C 2 -C 6 alkynyl;
C r C 6 alkylthio; C r C 6 haloalkylthio; C r C 6 alkylsulfmyl; C r C 6
alkylsulfonyl; C 3 -C 6 cycloalkyl; trimethylsilyl; C(=0)Rl4; C 2 -C 6
5 alkynyl substituted with trimethylsilyl or C 3 -C 6 cycloalkyl; or phenyl or
phenoxy, each phenyl or phenoxy optionally substituted with R 12 and
optionally substituted with one or more R 13 ;
each RlO i s halogen, C r C 6 alkyl, C r C 6 haloalkyl, C r C 6 alkoxy, Cj-C 6
haloalkoxy, cyano or thiocyanato; or
10 r9 and an R 10 when attached to adjacent carbon atoms can be taken together
as -CH 2 CH 2 0- or -OCH 2 CH 2 0-;
each R 1 1 is independently H, C r C 3 alkyl or cyclopropyl;
R 12 is halogen, C r C 6 alkyl, C r C 6 haloalkyl, C r C 6 alkoxy,
C r C 6 haloalkoxy, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl,
C r C 6 alkylthio, C r C 6 haloalkylthio, C r C 6 alkylsulfmyl, C r C 6
alkylsulfonyl, nitro, C(=0)R 14 or C 3 -C 6 cycloalkyl;
each R13 i s halogen, C r C 6 alkyl, C r C 6 haloalkyl, C r C 6 alkoxy, C r C 6
haloalkoxy, cyano or thiocyanato;
R 14 is H, C r C 6 alkyl, C r C 6 haloalkyl, C r C 6 alkoxy, C r C 6 haloalkoxy; and
20 risl,2, 3 or 4.
3 . A compound of Claim 2 wherein
TisTl;
R 3 is methyl; and
Z is phenyl optionally substituted with R 9 and optionally substituted with one
25 or m °re R!0; or a 5 or 6-membered aromatic heterocyclic ring, each
heterocyclic ring containing 1 to 4 heteroatoms independently selected
from the group nitrogen, oxygen, and sulfur, provided that each
heterocyclic ring contains no more than 3 nitrogens, no more than 1
oxygen, and no more than 1 sulfur, each aromatic heterocyclic ring
optionally substituted with R 9 and optionally substituted with one or
more R 10
4. A compound of Claim 3 wherein
A is N;
G is N;
35 w is O;
X is ORi;
R 1 is methyl; and
R 2 is methyl.
30
WO 99/28305
PCT/US98/24265
153
5. A compound of Claim 2 wherein
T is T2;
R 3 is methyl; and
Z is phenyl optionally substituted with R 9 and optionally substituted with one
or more R 10 ; or a 5 or 6-membered aromatic heterocyclic ring, each
heterocyclic ring containing 1 to 4 heteroatoms independently selected
from the group nitrogen, oxygen, and sulfur, provided that each
heterocyclic ring contains no more than 3 nitrogens, no more than 1
oxygen, and no more than 1 sulfur, each aromatic heterocyclic ring
optionally substituted with R 9 and optionally substituted with one or
more R 10 .
6 . A compound of Claim 2 wherein
T is T3;
R 3 is methyl; and
Z is phenyl optionally substituted with R 9 and optionally substituted with one
or more R ] 0; or a 5 or 6-membered aromatic heterocyclic ring, each
heterocyclic ring containing 1 to 4 heteroatoms independently selected
from the group nitrogen, oxygen, and sulfur, provided that each
heterocyclic ring contains no more than 3 nitrogens, no more than 1
oxygen, and no more than 1 sulfur, each aromatic heterocyclic ring
optionally substituted with R 9 and optionally substituted with one or
more R 10 .
7. A compound of Claim 2 wherein
T is T4;
R 3 is methyl; and
Z is phenyl optionally substituted with R 9 and optionally substituted with one
or more R 10 ; or a 5 or 6-membered aromatic heterocyclic ring, each
heterocyclic ring containing 1 to 4 heteroatoms independently selected
from the group nitrogen, oxygen, and sulfur, provided that each
heterocyclic ring contains no more than 3 nitrogens, no more than 1
oxygen, and no more than 1 sulfur, each aromatic heterocyclic ring
optionally substituted with R 9 and optionally substituted with one or
more R 10 .
8. The compound of Claim 7 which is selected from the group:
a-(methoxyimino)-A/;2-dimethyl-5-[[[[l-[3-
(trifluoromethyl)phenyl]ethylidene]amino]oxy]methyl]benzeneacetamideand
a-(methoxyimino)-A^,2-dimethyl-5-[[t[l-[3-
(trifluoromemoxy)phenyl]emylidene]amino]oxy]methyl]benzeneacetamide.
WO 99/28305
PCT/US98/24265
154
9. A fungicidal composition comprising a fungicidally effective amount of a
compound of Claim 1 and at least one of a surfactant, a solid diluent or a liquid diluent.
1 0. A method for controlling plant diseases caused by fungal plant pathogens
comprising applying to the plant or portion thereof, or to the plant seed or seedling, a
fungicidally effective amount of a compound of Claim 1.
11. An arthropodicidal composition comprising an arthropodicidally effective
amount of a compound of Claim 1 and at least one of a surfactant, a solid diluent or a liquid
diluent.
12. A method for controlling arthropods comprising contacting the arthropods or
their environment with an arthropodicidally effective amount of a compound of Claim 1.
13. A compound selected from Formula II
T
II
wherein
Tis
\2
^N^COOR5 R1 °^N^CONR6r5
T 3 or T4 .
X is ORi, S(0) m Ri or halogen;
A is O, S, N,NR5 orCR7;
G is C or N; provided that when G is C, A is O, S or NR 5 and the floating double bond
is attached to G; and when G is N, A is N or CR 7 and the floating double bond is
attached to A;
W is O or S;
Yl is OH, SH, OS0 2 CH 3 , OS0 2 (4-CH 3 -Ph), CHO, CH(RH)OH, CH(R")C1,
CH(R1 l)Br, CH(R1 1)1, CH(Rl l)OS0 2 CH 3 or CH(Rl 1 )OS0 2 (4-CH 3 -Ph);
WO 99/28305
PCT/US98/24265
155
Rl i s Ci-C 6 alkyl, C r C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl,
C 2 -C 6 haloalkynyl, C 3 -C 6 cycloalkyl, C 2 -C 4 alkylcarbonyl or C 2 -C 4
alkoxycarbonyl;
R 2 , R 5 and R 6 are each independently selected from the group H, C r C 6 alkyl, C r C 6
haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl,
C 3-C6 cycloalkyl, C 2 -C 4 alkylcarbonyl and C 2 -C 4 alkoxycarbonyl;
R 3 is halogen, CF 3 , C r C 3 alkyl or C,-C 3 alkoxy;
R 4 is H, halogen, CF 3 , C r C 3 alkyl or C r C 3 alkoxy;
R 7 is H, halogen or methyl;
R 11 is H, C r C 3 alkyl or cyclopropyl;
m is 0, 1 or 2; and
s is 0 or 1 ;
provided that when A is N, G is N, X is S(0) m Ri and m is 0, then is other than
haloalkyl.
INTERNATIONAL SEARCH REPORT
Interns tl Application No
PCT/US 98/24265
A. CLASSIFICATION OF SUBJECT MATTER
IPC 6 C07D249/12 A01N43/653 C07D417/12 C07C251/40
According to International Patent Classification (IPC) or to both national classification and IPC
8. FIELDS SEARCHED
Minimum documentation searched (classification system followed by classification symbols)
IPC 6 C07D AGIN C07C
Documentation searched other than minimum documentation to the extent that suoh documents are included In the fields searched
Electronic data base consulted during the international search (name of data base and, where practical, search terms used)
C. DOCUMENTS CONSIDERED TO BE RELEVANT
Category 0 Citation of dooument, with indication, where appropriate, of the relevant passages
Relevant to oiaim No.
WO 96 36615 A (DU PONT ; BROWN RICHARD
JAMES (US); SUN KING MO (US); FRASIER
DEBOR) 21 November 1996
see the whole document
US 5 194 662 A (BRAND SI EGBERT ET AL)
16 March 1993
cited in the application
see table IV
US 5 286 750 A (MUELLER BERND ET AL)
15 February 1994
cited in the application
see the whole document
EP 0 178 826 A (I CI PLC) 23 April 1986
cited in the application
see the whole document
2-13
2-13
2-13
2-13
□
Further doouments are listed In the continuation of box C.
Patent family members are listed in annex.
• Special categories of oited documents :
■A" document defining the general state of the art which is not
considered to be of particular relevance
"E" earlier dooument but published on or after the international
filing date
"L" document whioh may throw doubts on priority olaim(s) or
whioh is cited to establish the publication dote of another
oitatjon or other speoial reason (as specified)
"O" document referring to an oral disclosure, use, exhibition or
other means
"P" dooument published prior to the international filing data but
later than the priority date claimed
*T* later dooument published after the international filing date
or priority date and not in conflict with the application but
cited to understand the principle or theory underlying the
invention
"X* document of particular relevance; the oiaimed invention
cannot be considered novel or cannot be considered to
involve an Inventive step when the dooument is taken alone
"Y" dooument of particular relevanoe; the claimed invention
cannot be considered to involve an inventive stap when the
dooument is combined with one or more other such doau-
menta, such combination being obvious to a person skilled
in the art.
'&* document member of the same patent family
Date of the actual completion of the international aearoh
18 February 1999
Date of mailing of the international search report
03. 03.99
Name and mailing address of the ISA
European Patent Office, P.B. 581 8 Patentlaan 2
NL - 2280 HV Rijswijt
Tel. (+31-70) 340-2040, Tx. 31 651 epo nl,
Fax: (+31-70) 340-3016
Authorized offloer
Lauro, P
Form PCT/ISA/210 (second shea!) (July 1832)
INTERNATIONAL SEARCH REPORT
Intei.. ational application No.
PCT/US 98/24265
Box I Observations where certain claims were found unsearchable (Continuation of item 1 of first sheet)
This International Search Report has not been established in respect of certain claims under Article 17(2)(a) for the following reasons:
1 . Claims Nos.:
because they relate to subject matter not required to be searched by this Authority, namely:
2. Claim3 Nos.: 1
because they relate to parts of the International Application that do not comply with the prescribed requirements to such
an extent that no meaningful International Search can be carried out, specifically:
The subject-matter of claim 1 is obscure due to the unclear definition of the
group Y-Z
3. | | Claims Nos.:
beoause they are dependent claims and are not drafted in accordance with the second and third sentences of Rule 6.4(a).
Box II Observations where unity of Invention is lacking (Continuation of item 2 of first sheet)
This International Searching Authority found multiple inventions in this international application, as follows:
1 . I As all required additional search fees were timely paid by the applicant, this International Search Report covers ail
' ' searohable claims.
2. | | As all searchable claims could be searched without effort justifying an additional fee, this Authority did not invite payment
of any additional fee.
3. I As only some of the required additional search fees were timely paid by the applicant, this International Search Report
' ' covers only those claims for which fees were paid, specifically claims Nos. :
4. [ ] No required additional searoh fees were timely paid by the applicant. Consequently, this International Search Report is
restricted to the invention first mentioned in the claims; it is covered by claims Nos.:
Remark on Protest | [ The additional search fees were accompanied by the applicant's protest.
j No protest accompanied the payment of additional search fees.
Form PCT/1SA/21 0 (continuation of first sheet (1)) (July 1992)
INTERNATIONAL SEARCH REPORT
Information on patent (amity members
lntern.< al Application No
PCT/US 98/24265
Patent document
cited in search report
Publication
date
Patent family
member(s)
Publication
date
WO 9636615 A
21-11-1996
JP
10504042
T
14-04-1998
US 5194662 A
16-03-1993
DE
4020384
A
02-01-1992
DE
4020388
A
02-01-1992
AT
161007
T
15-12-1997
AT
170511
T
15-09-1998
AU
652159
B
18-08-1994
AU
7929691
A
28-01-1993
CA
2045725
A
28-12-1991
CS
9101966
A
19-02-1992
DE
59108900
D
22-01-1998
DE
59109047
D
08-10-1998
DK
\J IN
463488
T
12-01-1998
FP
Lr
0463488
U«J"TwU
A
02-01-1992
EP
0669319
A
30-08-1995
ES
2110421
T
16-02-1998
ES
2120100
T
16-10-1998
GR
3026148
T
29-05-1998
Hll
209642
B
28-09-1994
IL
98626
A
27-11-1995
JP
4261147
A
17-09-1992
NZ
238714
A
26-07-1994
US
5387607
A
07-02-1995
US
5563168
A
08-10-1996
US
5292759
A
08-03-1994
US 5286750 A 15-02-1994
DE
3933891
A
18-04-1991
AT
140691
T
15-08-1996
AU
642165
B
14-10-1993
AU
6394690
A
18-04-1991
CA
2027306
A
12-04-1991
DE
59010426
D
29-08-1996
DK
422597
T
26-08-1996
EP
0422597
A
17-04-1991
ES
2090073
T
16-10-1996
GR
3020744
T
30-11-1996
HU
210110
B
28-02-1995
IL
95945
A
19-01-1996
JP
3157350
A
05-07-1991
EP 0178826 A 23-04-1986
Form PCT/ISA/210 (patent family annex) (July 1992)
AU
588254
B
14-09-1989
AU
4823885
A
24-04-1986
BR
8505143
A
29-07-1986
CN
1008055
B
23-05-1990
CZ
8507456
A
15-02-1995
CZ
8707553
A
16-11-1994
DD
241998
A
14-01-1987
DD
260491
A
28-09-1988
DE
3584937
A
30-01-1992
DK
479285
A
20-04-1986
EP
0431328
A
12-06-1991
GB
2172595
A,B
24-09-1986
GB
2202843
A,B
05-10-1988
GB
2202844
A,B
05-10-1988
GB
2208647
A,B
12-04-1989
GR
852517
A
17-01-1986
HK
794
A
14-01-1994
HK
3194
A
21-01-1994
page 1 of 2
INTERNATIONAL SEARCH REPORT
Information on patent family members
Interna .al Application No
PCT/US 98/24265
Patent document
cited in search report
Publication
date
EP 0178826
Patent family
member(s)
Publication
date
HK
78192
A
23-10-1992
HK
133993
A
17-12-1993
HK
134093
A
17-12--1993
IE
58924
B
01-12-1993
JP
2551555
B
06-11-1996
JP
61106538
A
24-05-1986
LT
2162
R
15-10-1993
LT
960
A,B
27-03-1995
1 w
A
M
1U-UO— 13 30
LV
10239
A,B
20-10-1994
LV
5217
A
10-10-1993
PT
81321
B
17-02-1988
SK
745685
A
04-09-1996
SU
1819259
A
30-05-1993
SU
1600628
A
15-10-1990
RU
2044723
C
27-09-1995
US
5315025
A
24-05-1994
US
5286894
A
15-02-1994
Foim PCT/ISA/ZtO (palont family annax) (July 1992)
page 2 of 2
Live Music Archive
Librivox Free Audio
Metropolitan Museum
Cleveland Museum of Art
Internet Arcade
Console Living Room
Books to Borrow
Open Library
TV News
Understanding 9/11